Publication: CD36 polymorphism is associated with protection from cerebral malaria
Issued Date
2003-02-01
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ISSN
00029297
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2-s2.0-0037318894
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Mahidol University
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SCOPUS
Bibliographic Citation
American Journal of Human Genetics. Vol.72, No.2 (2003), 364-374
Suggested Citation
Kazuya Omi, Jun Ohashi, Jintana Patarapotikul, Hathairad Hananantachai, Izumi Naka, Sornchai Looareesuwan, Katsushi Tokunaga CD36 polymorphism is associated with protection from cerebral malaria. American Journal of Human Genetics. Vol.72, No.2 (2003), 364-374. doi:10.1086/346091 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/20767
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Title
CD36 polymorphism is associated with protection from cerebral malaria
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Abstract
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.