Browsing by Author "Jintana Patarapotikul"

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    Absence of association between the allele coding methionine at position 29 in the N-terminal domain of ICAM-1 (ICAM-1Kilifi) and severe malaria in the northwest of Thailand
    (2001-10-08) Jun Ohashi; Izumi Naka; Jintana Patarapotikul; Hathairad Hananantachai; Sornchai Looareesuwan; Katsushi Tokunaga; University of Tokyo; Mahidol University
    Intercellular adhesion molecule 1 (ICAM-1) is known to be the endothelial receptor for Plasmodium falciparum-infected erythrocytes. Associations of the variant allele coding methionine at position 29 in the N-terminal domain of ICAM-1, ICAM-1Kilifi, with severe malaria have been investigated in African populations, and the results of these investigations have varied widely. In this study, we investigated a possible association between the ICAM-1Kilifi and severe malaria in adult malaria patients living in northwest Thailand. The frequencies of the ICAM-1Kilifi among patients with mild malaria, with non-cerebral severe malaria, and with cerebral malaria were 1.7%, 2.7%, and 2.3%, respectively. This variant showed neither positive nor negative association with severe malaria in Thailand.
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    Absence of association between the Fcγ receptor IIIA-176F\ V polymorphism and the severity of malaria in Thai
    (2002-10-01) Kazuya Omi; Jun Ohashi; Jintana Patarapotikul; Hathairad Hananantachai; Izumi Naka; Sornchai Looareesuwan; Katsushi Tokunaga; Mahidol University; University of Tokyo
    Human Fcγ receptor (FcγR) genes form a clustered gene family, which consists of Fcγ RIIA, IIB, IIC, IIIA, and IIIB genes, on chromosome 1q23. We previously reported that the Fcγ RIIA-131H/H genotype in combination with the FcγRIIIB-NA2 allele is associated with susceptibility to cerebral malaria, and that such an association can be caused by linkage disequilibrium (LD) between these polymorphisms and the primary associated gene(s) in this region. FcγRIIIA is known to exhibit the genetic polymorphism FcγRIIIA-176F/V coded for different affinity to IgG1 and IgG3. In this study, we examined a possible association between FcγRIIIA-176F/V polymorphism and severity of malaria in 462 adult Thai patients with Plasmodium falciparum malaria. The frequencies of FcγRIIIA-176V among patients with mild malaria, with non-cerebral severe malaria, and with cerebral malaria were 32.7%, 29.9%, and 36.3%, respectively. This polymorphism showed neither positive nor negative association with the severity of malaria. Thus, we concluded that the association of FcγRIIA-131H/R and FcγRIIIB-NA1/NA2 polymorphisms with cerebral malaria in Thailand is not due to the LD caused by FcγRIIIA-176F/V.
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    Antibody-Enhanced Binding of Dengue-2 Virus to Human Platelets
    (1995-10-20) Songli Wang; Runtao He; Jintana Patarapotikul; Bruce L. Innis; Robert Anderson; Dalhousie University; Mahidol University; Armed Forces Research Institute of Medical Sciences, Thailand; Walter Reed Army Institute of Research
    The mechanisms underlying severe thrombocytopenia in dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) are not completely understood. We present here the first evidence that dengue type 2 virus binds to human platelets only in the presence of virus-specific antibody, supporting a role for immune-mediated clearance of platelets in the pathogenesis of thrombocytopenia in DHF/DSS. Antibody-enhanced binding of virus of platelets was also demonstrated with a panel of eight murine monoclonal antibodies specific for the dengue E protein. The degree of binding was dependent on the antibody used but not on the antibody IgG subclass, indicating that factors other than the platelet Fc receptor are involved in binding of virus-antibody complexes to the platelet surface. Confirmation that antibody-dependent virus binding to platelets is not primarily mediated by the platelet Fc receptor was obtained by demonstrating good binding even when platelets were pretreated with the FcγRII-specific antibody IV.3. © 1995 Academic Press. All rights reserved.
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    Association of ADAMTS13 polymorphism with cerebral malaria
    (2011-12-15) Sirima Kraisin; Izumi Naka; Jintana Patarapotikul; Duangdao Nantakomol; Pornlada Nuchnoi; Hathairad Hananantachai; Naoyuki Tsuchiya; Jun Ohashi; University of Tsukuba; Chulalongkorn University; Mahidol University
    Background: Cerebral malaria is one of the most severe manifestations of Plasmodium falciparum malaria. The sequestration of parasitized red blood cells (PRBCs) to brain microvascular endothelium has been shown to contribute to the pathophysiology of cerebral malaria. Recent studies reported increased levels of von Willebrand factor (VWF) and reduced activity of VWF-cleaving protease, ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), in patients with cerebral malaria. Methods. Association of six single nucleotide polymorphisms (SNPs) of the ADAMTS13 gene with cerebral malaria was examined in 708 Thai patients with P. falciparum malaria. Results: Among six SNPs, the derived allele of a SNP located in intron 28, rs4962153-A, was significantly associated with protection against cerebral malaria when 115 cerebral malaria patients were compared with 367 mild malaria patients (Fisher's exact P-value = 0.0057; OR = 0.27; 95% CI = 0.096-0.76). Significant association was also detected between 115 cerebral malaria and 593 non-cerebral malaria (226 non-cerebral severe malaria and 367 mild malaria) patients (Fisher's exact P-value = 0.012; OR = 0.30; 95% CI = 0.11-0.83). Conclusions: Excessive adhesion of PRBCs to the platelet-decorated ultra-large VWF (ULVWF) appears to enhance the sequestration of PRBCs to cerebral microvascular endothelium. The genetic association observed in the present study implies that the regulation of platelet-decorated ULVWF strings by ADAMTS13 may play a role in the development of cerebral malaria. © 2011 Kraisin et al; licensee BioMed Central Ltd.
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    Association of BAK1 single nucleotide polymorphism with a risk for dengue hemorrhagic fever
    (2016-07-11) Tran Ngoc Dang; Izumi Naka; Areerat Sa-Ngasang; Surapee Anantapreecha; Nuanjun Wichukchinda; Pathom Sawanpanyalert; Jintana Patarapotikul; Naoyuki Tsuchiya; Jun Ohashi; University of Tsukuba; University of Medicine and Pharmacy Vietnam; University of Tokyo; Thailand Ministry of Public Health; The Food and Drug Administration, Thailand Ministry of Public Health; Mahidol University
    © 2016 The Author(s). Background: Dengue hemorrhagic fever (DHF) is a severe life-threatening form of dengue infection. Low platelet count is one of the characteristic clinical manifestations in patients with severe dengue. However, little is known about genetic factors in the host that cause low platelet count in patients with dengue. Methods: A previous genome-wide association study of hematological and biochemical traits identified single nucleotide polymorphisms (SNPs) associated with low platelet count in healthy subjects. To examine the possible association of these SNPs with DHF, 918 Thai patients with dengue [509 patients with DHF and 409 with dengue fever (DF)] were genotyped for five SNPs: rs5745568 in BAK1, rs6141 in THPO, rs6065 in GP1BA, rs739496 in SH2B3, and rs385893 in RCL1. In addition, rs4804803 in CD209, that has been reported to be associated with dengue infection, was also genotyped to examine if rs4804803 affects the association detected in this study. Results: The allele frequencies of each SNP were compared between the DHF and DF groups. Among the five SNPs, the G allele of rs5745568 in BAK1 was significantly associated with a risk for DHF [P = 0.006 and crude odd ratio (95 % confidence interval) = 1.32 (1.09-1.60)]. The association of this allele with DHF was also significant in a logistic regression analysis adjusted for age, sex, hospital (i.e., geographic region), immune status (i.e., primary or secondary infection), and virus serotype [P = 0.016 and adjusted odd ratio (95 % confidence interval) = 1.29 (1.05-1.58)]. The result was not influenced by rs4804803 [P = 0.0167 and adjusted OR (95 % CI) = 1.29 (1.05-1.58)]. No other SNPs including rs4804803 showed significant association. Conclusions: The low-level constitutive production of platelets caused by the G allele of rs5745568 seems to increase the risk of bleeding in dengue infection. Our results suggest that BCL-2 homologous antagonist/killer (BAK) protein, encoded by BAK1, plays a crucial role in the pathogenesis of DHF.
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    Association of IL1B -31C/T and IL1RA variable number of an 86-bp tandem repeat with dengue shock syndrome in Thailand
    (2014-07-01) Areerat Sa-Ngasang; Jun Ohashi; Izumi Naka; Surapee Anantapreecha; Pathom Sawanpanyalert; Jintana Patarapotikul; Mahidol University; Thailand Ministry of Public Health; University of Tsukuba; The Food and Drug Administration, Thailand Ministry of Public Health
    Background. Dengue patients present a range of symptoms: dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS). It is not clear whether this variability is due to their genetic background. Here we tested polymorphisms of interleukin 1 beta (IL1B) and interleukin 1 receptor antagonist (IL1RA) genes for association with DSS in the Thai population. Methods. Polymorphisms of IL1B -31C/T (rs1143627) and IL1RA 86-base-pair tandem repeat were analyzed in 871 patients (DF = 384, DHF = 413, and DSS = 74). Results. IL1B -31C and IL1RA 2/4 genotype were associated with DSS (IL1B -31C: DSS vs DHF: P = .0061, odds ratio [OR, 95% confidence interval {CI}], 3.49 [1.36-8.95]; DSS vs DF: P = .027, OR [95% CI], 2.81 [1.12-7.06]; IL1RA 2/4: DSS vs DHF: P = .017, OR [95% CI], 1.94 [1.12-3.40]; DSS vs DF: P = .024, OR [95% CI], 1.90 [1.07-3.4]). No difference was found between DF and DHF. Logistic regression analysis revealed that IL1B -31C and IL1RA 2/4 genotypes were each independently associated with DSS. Conclusions. Patients with IL1B -31C carrier, or IL1RA 2/4 genotype carry a risk for DSS, implying that IL1B may play a role in pathogenesis of DSS.
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    Association of PECAM1/CD31 polymorphisms with cerebral malaria
    (2016-01-01) Jun Ohashi; Izumi Naka; Hathairad Hananantachai; Jintana Patarapotikul; University of Tokyo; University of Tsukuba; Mahidol University
    © E-Century Publishing Corporation. All rights reserved. Platelet/endothelial cell adhesion molecule-1 (PECAM1/CD31), a receptor recognized by P. falciparum-infected red blood cells (iRBCs), on the vascular endothelium has been implicated in mediating cytoadherence in patients with P. falciparum malaria. To examine associations of PECAM1 polymorphisms with cerebral malaria, 11 tag single nucleotide polymorphisms (SNPs) of PECAM1 were analysed for 312 Thai patients with P. falciparum malaria (109 with cerebral malaria and 203 with mild malaria). The rs1122800-C allele was significantly associated with protection from cerebral malaria (P = 0.017), and the rs9912957-A significantly increased the risk for cerebral malaria (P = 0.0065) in malaria patients. Fine-scale mapping using genotyped and imputed SNPs and linkage disequilibrium (LD) analysis revealed that rs1122800 and rs9912957 were located in two distinct LD blocks and were independently associated with cerebral malaria. The rs1122800-C allele was significantly associated with lower expression level of PECAM1 in EBV-transformed lymphoblastoid cell lines (P = 0.045). The present results suggest that PECAM1-mediated cytoadherence of iRBCs to brain endothelium plays a crucial role in the pathogenesis of cerebral malaria.
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    Association of the endothelial protein C receptor (PROCR) rs867186-G allele with protection from severe malaria
    (2014-03-17) Izumi Naka; Jintana Patarapotikul; Hathairad Hananantachai; Hiroo Imai; Jun Ohashi; University of Tsukuba; Mahidol University; Kyoto University
    Background: Cytoadhesion of Plasmodium falciparum-infected erythrocytes to endothelial cells in microvessels is a remarkable characteristic of severe malaria. The endothelial protein C receptor (EPCR), encoded by the endothelial protein C receptor gene (PROCR), has recently been identified as an endothelial receptor for specific P. falciparum erythrocyte membrane protein 1 (PfEMP1) subtypes containing domain cassettes (DCs) 8 and 13. The PROCR rs867186-G allele (serine-to-glycine substitution at position 219 of EPCR; 219Gly) has been shown to be associated with higher levels of plasma soluble EPCR (sEPCR). In this study, the association of PROCR rs867186 with severe malaria is examined in Thai population. Methods. A total of 707 Thai patients with P. falciparum malaria (341 with severe malaria and 336 with mild malaria) were genotyped for rs867186. To assess the association of PROCR rs867186 with severe malaria, three models (dominant, recessive and allelic) were evaluated. The rates of non-synonymous and synonymous substitutions were estimated for the coding sequence of the PROCR gene. Results: The rs867186-GG genotype was significantly associated with protection from severe malaria (P-value = 0.026; odds ratio = 0.33; 95% confidence interval = 0.12-0.90). Evolutionary analysis provided no evidence of strong positive selection acting on the PROCR gene. Conclusion: The rs867186-GG genotype showed significant association with protection from severe malaria. The present results suggest that PfEMP1-EPCR interaction, which can mediate cytoadhesion and/or reduce cytoprotective and anti-inflammatory effects, is crucial to the pathogenesis of severe malaria. © 2014 Naka et al.; licensee BioMed Central Ltd.
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    CD36 polymorphism is associated with protection from cerebral malaria
    (2003-02-01) Kazuya Omi; Jun Ohashi; Jintana Patarapotikul; Hathairad Hananantachai; Izumi Naka; Sornchai Looareesuwan; Katsushi Tokunaga; University of Tokyo; Mahidol University
    The human protein CD36 is a major receptor for Plasmodium falciparum-infected erythrocytes and contributes to the pathology of P. falciparum malaria. We performed variation screening of the CD36 gene and examined the possible association between CD36 polymorphisms and the severity of malaria in 475 adult Thai patients with P. falciparum malaria. Accordingly, we identified nine CD36 polymorphisms with a high-frequency (>15%) minor allele. Of these, the frequencies of the - 14T→C allele in the upstream promoter region and the - 53G→T allele in the downstream promoter region were significantly decreased in patients with cerebral malaria compared to those with mild malaria (P = .016 for - 14T→C and P = .050 for - 53G→T). The analysis of linkage disequilibrium (LD) between the nine common polymorphisms revealed that there are two blocks with strong LD in the CD36 gene and that the - 14T→C and - 53G→T polymorphisms are within the upstream block of 35 kb from the upstream promoter to exon 8. Further association testing after the second variation screening in the upstream block indicated that the in3(TG)12(i.e., 12 TG repeats in intron 3) allele is most strongly associated with the reduction in the risk of cerebral malaria (odds ratio 0.59; 95% confidence interval 0.40-0.87; P = .0069). We found, by reverse-transcriptase PCR amplification, that in3(TG)12is involved in the nonproduction of the variant CD36 transcript that lacks exons 4 and 5. Since exon 5 of the gene is known to encode the ligand-binding domain for P. falciparum-infected erythrocytes, in3(TG)12itself or a primary variant on the haplotype with in3(TG)12may be responsible for protection from cerebral malaria in Thailand. Results of the present study suggest that LD mapping has potential for detecting a disease-associated variant on the basis of haplotype blocks.
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    Diversifying selection on the thrombospondin-related adhesive protein (TRAP) gene of plasmodium falciparum in Thailand
    (2014-02-28) Jun Ohashi; Yuji Suzuki; Izumi Naka; Hathairad Hananantachai; Jintana Patarapotikul; University of Tsukuba; Mahidol University
    Sporozoites of Plasmodium falciparum are transmitted to human hosts by Anopheles mosquitoes. Thrombospondin-related adhesive protein (TRAP) is expressed in sporozoites and plays a crucial role in sporozoite gliding and invasion of human hepatocytes. A previous study showed that the TRAP gene has been subjected to balancing selection in the Gambian P. falciparum population. To further study the molecular evolution of the TRAP gene in Plasmodium falciparum, we investigated TRAP polymorphisms in P. falciparum isolates from Suan Phueng District in Ratchaburi Province, Thailand. The analysis of the entire TRAP coding sequences in 32 isolates identified a total of 39 single nucleotide polymorphisms (SNPs), which comprised 37 nonsynonymous and two synonymous SNPs. McDonald-Kreitman test showed that the ratio of the number of nonsynonymous to synonymous polymorphic sites within P. falciparum was significantly higher than that of the number of nonsynonymous to synonymous fixed sites between P. falciparum and P. reichenowi. Furthermore, the rate of nonsynonymous substitution was significantly higher than that of synonymous substitution within Thai P. falciparum. These results indicate that the TRAP gene has been subject to diversifying selection in the Thai P. falciparum population as well as the Gambian P. falciparum population. Comparison of our P. falciparum isolates with those from another region of Thailand (Tak province, Thailand) revealed that TRAP was highly differentiated between geographically close regions. This rapid diversification seems to reflect strong recent positive selection on TRAP. Our results suggest that the TRAP molecule is a major target of the human immune response to pre-erythrocytic stages of P. falciparum. © 2014 Ohashi et al. This.
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    Dynamic RNA profiling in Plasmodium falciparum synchronized blood stages exposed to lethal doses of artesunate
    (2008-08-18) Onguma Natalang; Emmanuel Bischoff; Guillaume Deplaine; Caroline Proux; Marie Agnès Dillies; Odile Sismeiro; Ghislaine Guigon; Serge Bonnefoy; Jintana Patarapotikul; Odile Mercereau-Puijalon; Jean Yves Coppée; Peter H. David; CNRS Centre National de la Recherche Scientifique; Institut Pasteur, Paris; Mahidol University
    Background: Translation of the genome sequence of Plasmodium sp. into biologically relevant information relies on high through-put genomics technology which includes transcriptome analysis. However, few studies to date have used this powerful approach to explore transcriptome alterations of P. falciparum parasites exposed to antimalarial drugs. Results: The rapid action of artesunate allowed us to study dynamic changes of the parasite transcriptome in synchronous parasite cultures exposed to the drug for 90 minutes and 3 hours. Developmentally regulated genes were filtered out, leaving 398 genes which presented altered transcript levels reflecting drug-exposure. Few genes related to metabolic pathways, most encoded chaperones, transporters, kinases, Zn-finger proteins, transcription activating proteins, proteins involved in proteasome degradation, in oxidative stress and in cell cycle regulation. A positive bias was observed for over-expressed genes presenting a subtelomeric location, allelic polymorphism and encoding proteins with potential export sequences, which often belonged to subtelomeric multi-gene families. This pointed to the mobilization of processes shaping the interface between the parasite and its environment. In parallel, pathways were engaged which could lead to parasite death, such as interference with purine/pyrimidine metabolism, the mitochondrial electron transport chain, proteasome-dependent protein degradation or the integrity of the food vacuole. Conclusion: The high proportion of over-expressed genes encoding proteins exported from the parasite highlight the importance of extra-parasitic compartments as fields for exploration in drug research which, to date, has mostly focused on the parasite itself rather than on its intra and extra erythrocytic environment. Further work is needed to clarify which transcriptome alterations observed reflect a specific response to overcome artesunate toxicity or more general perturbations on the path to cellular death. © 2008 Natalang et al; licensee BioMed Central Ltd.
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    Evolution of Fseg/Cseg dimorphism in region III of the Plasmodium falciparum eba-175 gene
    (2017-04-01) Yoshiki Yasukochi; Izumi Naka; Jintana Patarapotikul; Hathairad Hananantachai; Jun Ohashi; Mie University; University of Tokyo; Mahidol University
    © 2017 Elsevier B.V. The 175-kDa erythrocyte binding antigen (EBA-175) of the malaria parasite Plasmodium falciparum is important for its invasion into human erythrocytes. The primary structure of eba-175 is divided into seven regions, namely I to VII. Region III contains highly divergent dimorphic segments, termed Fseg and Cseg. The allele frequencies of segmental dimorphism within a P. falciparum population have been extensively examined; however, the molecular evolution of segmental dimorphism is not well understood. A comprehensive comparison of nucleotide sequences among 32 P. falciparum eba-175 alleles identified in our previous study, two Plasmodium reichenowi, and one P. gaboni orthologous alleles obtained from the GenBank database was conducted to uncover the origin and evolutionary processes of segmental dimorphism in P. falciparum eba-175. In the eba-175 nucleotide sequence derived from a P. reichenowi CDC strain, both Fseg and Cseg were found in region III, which implies that the original eba-175 gene had both segments, and deletions of F- and C-segments generated Cseg and Fseg alleles, respectively. We also confirmed the presence of allele with Fseg and Cseg in another P. reichenowi strain (SY57), by re-mapping short reads obtained from the GenBank database. On the other hand, the segmental sequence of eba-175 ortholog in P. gaboni was quite diverged from those of the other species, suggesting that the original eba-175 dimorphism of P. falciparum can be traced back to the stem linage of P. falciparum and P. reichenowi. Our findings suggest that Fseg and Cseg alleles are derived from a single eba-175 allele containing both segments in the ancestral population of P. falciparum and P. reichenowi, and that the allelic dimorphism of eba-175 was shaped by the independent emergence of similar dimorphic lineage in different species that has never been observed in any evolutionary mode of allelic dimorphism at other loci in malaria genomes.
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    Extended linkage disequilibrium surrounding the hemoglobin E variant due to malarial selection
    (2004-01-01) Jun Ohashi; Izumi Naka; Jintana Patarapotikul; Hathairad Hananantachai; Gary Brittenham; Sornchai Looareesuwan; Andrew G. Clark; Katsushi Tokunaga; University of Tokyo; Cornell University; Mahidol University; Columbia University, College of Physicians and Surgeons
    The hemoglobin E variant (HbE;β26Glu→Lys) is concentrated in parts of Southeast Asia where malaria is endemic, and HbE carrier status has been shown to confer some protection against Plasmodium falciparum malaria. To examine the effect of natural selection on the pattern of linkage disequilibrium (LD) and to infer the evolutionary history of the HbE variant, we analyzed biallelic markers surrounding the HbE variant in a Thai population. Pairwise LD analysis of HbE and 43 surrounding biallelic markers revealed LD of HbE extending beyond 100 kb, whereas no LD was observed between non-HbE variants and the same markers. The inferred haplotype network suggests a single origin of the HbE variant in the Thai population. Forward-in-time computer simulations under a variety of selection models indicate that the HbE variant arose 1,240-4,440 years ago. These results support the conjecture that the HbE mutation occurred recently, and the allele frequency has increased rapidly. Our study provides another clear demonstration that a high-resolution LD map across the human genome can detect recent variants that have been subjected to positive selection.
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    Fcγ receptor IIA and IIIB polymorphisms are associated with susceptibility to cerebral malaria
    (2002-12-01) Kazuya Omi; Jun Ohashi; Jintana Patarapotikul; Hathairad Hananantachai; Izumi Naka; Sornchai Looareesuwan; Katsushi Tokunaga; University of Tokyo; Mahidol University
    Human FcγRIIA and FcγRIIIB exhibit genetic polymorphisms, FcγRIIA-131H/R and FcγRIIIB-NA1/NA2, coding for different capacities for IgG binding and phagocytosis. Recently, FcγRIIA-131R was reported to be associated with protection against high-density Plasmodium falciparum infection in Kenya. Furthermore, FcγRIIIB-NA1/NA2 polymorphism was shown to influence FcγRIIA function in an allele-specific manner. In this study, we examined a possible association of FcγRIIA-131H/R and FcγRIIIB-NA1/NA2 polymorphisms with malaria severity in 107 cerebral malaria patients, 157 non-cerebral severe malaria patients, and 202 mild malaria controls living in northwest Thailand. This study reveals that, with the FcγRIIIB-NA2 allele, the FcγRIIA-131H/H genotype is associated with susceptibility to cerebral malaria (OR 1.85, 95% CI 1.14-3.01; P=0.012), although these polymorphisms are not individually involved in the disease severity. Our results suggest that FcγRIIA-131H/R and FcγRIIIB-NA1/NA2 polymorphisms have an interactive effect on host defense against malaria infection. © 2002 Elsevier Science Ireland Ltd. All rights reserved.
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    FTO polymorphisms in oceanic populations
    (2007-12-01) Jun Ohashi; Izumi Naka; Ryosuke Kimura; Kazumi Natsuhara; Taro Yamauchi; Takuro Furusawa; Minato Nakazawa; Yuji Ataka; Jintana Patarapotikul; Pornlada Nuchnoi; Katsushi Tokunaga; Takafumi Ishida; Tsukasa Inaoka; Yasuhiro Matsumura; Ryutaro Ohtsuka; University of Tokyo; Tokai University; Fukuoka Prefectural University; Hokkaido University; Gunma University; Kwansei Gakuin University; Mahidol University; Saga University; National Institute of Health and Nutrition Tokyo; National Institute for Environmental Studies of Japan
    It has been suggested that Neel's "thrifty genotype" model may account for high body weights in some Oceanic populations, which presumably arose in modern times. In European populations, common variants (rs1421085-C, rs17817449-G, and rs9939609-A) in the fat mass and obesity (FTO associated) were recently found to be associated with body mass index (BMI) or obesity. In this study, we investigated the population frequencies of these variants in six Oceanic populations (Melanesians, Micronesians, and Polynesians) and tested for an association with BMI. Unlike European populations, the Oceanic populations displayed no significant association between the FTO polymorphisms and BMI. These variants were in strong linkage disequilibrium. The population frequencies ranged between 4.2 and 30.3% in the six Oceanic populations, and were similar to those in southeast and east Asian populations. Our study of the FTO polymorphisms has generated no evidence to support the thrifty genotype hypothesis for Oceanic populations. © 2007 The Japan Society of Human Genetics and Springer.
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    A functional polymorphism in the IL1B gene promoter, IL1B -31C>T, is not associated with cerebral malaria in Thailand
    (2005-08-14) Jun Ohashi; Izumi Naka; Akihiro Doi; Jintana Patarapotikul; Hathairad Hananantachai; Noppadon Tangpukdee; Sornchai Looareesuwan; Katsushi Tokunaga; University of Tokyo; Mahidol University
    Background: IL-1β and IL-1RA levels are higher in the serum of cerebral malaria patients than in patients with mild malaria. Recently, the level of IL1B expression was reported to be influenced by a polymorphism in the promoter of IL1, IL1B -31C>T. Methods: To examine whether polymorphisms in IL1B and IL1RA influence the susceptibility to cerebral malaria, IL1B -31C>T, IL1B 3953C>T, and IL1RA variable number of tandem repeat (VNTR) were analysed in 312 Thai patients with malaria (109 cerebral malaria and 203 mild malaria patients). Results: In this population, IL1B -31C>T and IL1RA VNTRwere detected, while IL1B 3953C>T (i.e., IL1B 3953T) was not observed in the polymorphism screening for 32 patients. Further analyses for IL1B -31C>T and IL1RA VNTR in 110 cerebral malaria and 206 mild malaria patients showed no significant association of these polymorphisms with cerebral malaria. Conclusion: The present results suggest that IL1B -31C>T and IL1RA VNTR polymorphisms do not play a crucial role in susceptibility or resistance to cerebral malaria. © 2005 Ohashi et al; licensee BioMed Central Ltd.
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    A functional polymorphism in the IL1B gene promoter, IL1B -31C>T, is not associated with cerebral malaria in Thailand.
    (2005-08-14) Ohashi, Jun; Naka, Izumi; Doi, Akihiro; Jintana Patarapotikul; จินตนา ภัทรโพธิกุล; Hathairad Hananantachai; Noppadon Tangpukdee; นพดล ตั้งภักดี; Sornchai Looareesuwan; ศรชัย หลูอารีย์สุวรรณ; Tokunaga, Katsushi; Mahidol University. Faculty of Tropical Medicine
    IL-1beta and IL-1RA levels are higher in the serum of cerebral malaria patients than in patients with mild malaria. Recently, the level of IL1B expression was reported to be influenced by a polymorphism in the promoter of IL1, IL1B -31C>T. METHODS: To examine whether polymorphisms in IL1B and IL1RA influence the susceptibility to cerebral malaria, IL1B -31C>T, IL1B 3953C>T, and IL1RA variable number of tandem repeat (VNTR) were analysed in 312 Thai patients with malaria (109 cerebral malaria and 203 mild malaria patients). RESULTS: In this population, IL1B -31C>T and IL1RA VNTR were detected, while IL1B 3953C>T (i.e., IL1B 3953T) was not observed in the polymorphism screening for 32 patients. Further analyses for IL1B -31C>T and IL1RA VNTR in 110 cerebral malaria and 206 mild malaria patients showed no significant association of these polymorphisms with cerebral malaria. CONCLUSION: The present results suggest that IL1B -31C>T and IL1RA VNTR polymorphisms do not play a crucial role in susceptibility or resistance to cerebral malaria.
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    A functional single-nucleotide polymorphism in the CR1 promoter region contributes to protection against cerebral malaria
    (2008-12-15) Phairote Teeranaipong; Jun Ohashi; Jintana Patarapotikul; Ryosuke Kimura; Pornlada Nuchnoi; Hathairad Hananantachai; Izumi Naka; Chaturong Putaporntip; Somchai Jongwutiwes; Katsushi Tokunaga; University of Tokyo; Tokai University School of Medicine; Mahidol University; Chulalongkorn University; Naresuan University; University of Tsukuba
    Background. Although the level of erythrocyte complement receptor type 1 (E-CR1) expression in patients with malaria has been extensively studied, whether the level of expression of E-CR1 is associated with severe malaria remains controversial. The present study examined a possible association of polymorphisms in the CR1 gene with the severity of malaria, and it evaluated the influence of the associated polymorphism on expression of E-CR1. Methods. Seventeen single-nucleotide polymorphisms in CR1 were genotyped in 477 Thai patients who had Plasmodium falciparum malaria (203 had mild malaria, 165 had noncerebral severe malaria, and 109 had cerebral malaria). The E-CR1 expression level was measured by flow cytometry in 24 healthy Thai subjects. Results. The T allele of the reference single-nucleotide polymorphism rs9429942 in the CR1 promoter region was strongly associated with protection against cerebral malaria (2.2% of patients with mild malaria vs. 7.8% of patients with cerebral malaria; P = .0009; Bonferroni-adjusted Pc= .0306). The E-CR1 expression level was significantly higher in individuals with the TT genotype of rs9429942 than in individuals with the TC genotype of rs9429942 (P = .0282). Conclusions. We identified a CR1 promoter allele, associated with higher E-CR1 expression, that conferred protection against cerebral malaria. Previous studies have shown that the rate of clearance of immune complexes (ICs) from the circulation is related to the E-CR1 level. These results lead to the hypothesis that the clearance of ICs regulated by E-CR1 therefore plays a crucial role in the pathogenesis of cerebral malaria. © 2008 by the Infectious Diseases Society of America. All rights reserved.
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    Genetic association study of interferon lambda 3, CD27, and human leukocyte antigen-DPB1 with dengue severity in Thailand
    (2020-12-01) Unchana Arayasongsak; Izumi Naka; Jun Ohashi; Jintana Patarapotikul; Pornlada Nuchnoi; Thareerat Kalambaheti; Areerat Sa-Ngasang; Sumalee Chanama; Suwanna Chaorattanakawee; The University of Tokyo; Mahidol University; National Institutes of Health (NIH)
    © 2020, The Author(s). Background: Dengue patients develop different disease severity ranging from mild (dengue fever [DF]) to severe forms (dengue hemorrhagic fever [DHF] and the fatal dengue shock syndrome [DSS]). Host genetics are considered to be one factor responsible for the severity of dengue outcomes. To identify genes associated with dengue severity that have not been studied yet, we performed genetic association analyses of interferon lambda 3 (IFNL3), CD27, and human leukocyte antigen-DPB1 (HLA-DPB1) genes in Thai dengue patients. Methods: A case–control association study was performed in 877 children (age ≤ 15 years) with dengue infection (DF, n = 386; DHF, n = 416; DSS, n = 75). A candidate single nucleotide polymorphism of each of IFNL3, CD27, and HLA-DPB1 was selected to be analyzed. Genotyping was performed by TaqMan real-time PCR assay, and the association with dengue severity was examined. Results: The rs9277534 variant of HLA-DPB1 was weakly associated with DHF. The genotype GG and G allele conferred protection against DHF (p = 0.04, odds ratio 0.74 for GG genotype, p = 0.03, odds ratio 0.79 for G allele). The association became borderline significant after adjusting for confounders (p = 0.05, odds ratio 0.82). No association was detected for IFNL3 or CD27. Conclusions: The present study demonstrated the weak association of the rs9277534 variant of HLA-DPB1 with protection against DHF. This variant is in the 3′ untranslated region and affects HLA-DPB1 surface protein expression. Our finding suggests that HLA-DPB1 may be involved in DHF pathogenesis.
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    Genetic evidence for contribution of human dispersal to the genetic diversity of EBA-175 in Plasmodium falciparum
    (2015-08-01) Yoshiki Yasukochi; Izumi Naka; Jintana Patarapotikul; Hathairad Hananantachai; Jun Ohashi; University of Tokyo; Mahidol University
    © 2015 Yasukochi et al. Background: The 175-kDa erythrocyte binding antigen (EBA-175) of Plasmodium falciparum plays a crucial role in merozoite invasion into human erythrocytes. EBA-175 is believed to have been under diversifying selection; however, there have been no studies investigating the effect of dispersal of humans out of Africa on the genetic variation of EBA-175 in P. falciparum. Methods: The PCR-direct sequencing was performed for a part of the eba-175 gene (regions II and III) using DNA samples obtained from Thai patients infected with P. falciparum. The divergence times for the P. falciparum eba-175 alleles were estimated assuming that P. falciparum/Plasmodium reichenowi divergence occurred 6 million years ago (MYA). To examine the possibility of diversifying selection, nonsynonymous and synonymous substitution rates for Plasmodium species were also estimated. Results: A total of 32 eba-175 alleles were identified from 131 Thai P. falciparum isolates. Their estimated divergence time was 0.13-0.14 MYA, before the exodus of humans from Africa. A phylogenetic tree for a large sequence dataset of P. falciparum eba-175 alleles from across the world showed the presence of a basal Asian-specific cluster for all P. falciparum sequences. A markedly more nonsynonymous substitutions than synonymous substitutions in region II in P. falciparum was also detected, but not within Plasmodium species parasitizing African apes, suggesting that diversifying selection has acted specifically on P. falciparum eba-175. Conclusions: Plasmodium falciparum eba-175 genetic diversity appeared to increase following the exodus of Asian ancestors from Africa. Diversifying selection may have played an important role in the diversification of eba-175 allelic lineages. The present results suggest that the dispersals of humans out of Africa influenced significantly the molecular evolution of P. falciparum EBA-175.