Browsing by Author "Gareth J. McKay"

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    The association between complement component 2/complement factor B polymorphisms and age-related macular degeneration: A HuGE review and meta-analysis
    (2012-09-01) Ammarin Thakkinstian; Mark McEvoy; Usha Chakravarthy; Subhabrata Chakrabarti; Gareth J. McKay; Euijung Ryu; Giuliana Silvestri; Inderjeet Kaur; Peter Francis; Takeshi Iwata; Masakazu Akahori; Astrid Arning; Albert O. Edwards; Johanna M. Seddon; John Attia; Mahidol University; University of Newcastle, Australia; Queen's University Belfast; L.V. Prasad Eye Institute India; Mayo Clinic; OHSU School of Medicine; National Hospital Organization, Japan; Leibniz Institute of Arteriosclerosis Research; University of Oregon; Tufts University School of Medicine; John Hunter Hospital
    The authors performed a systematic review of the association of complement component 2(C2)/complement factor B (CFB) gene polymorphisms with age-related macular degeneration (AMD). In total, data from 19 studies published between 2006 and 2011 were pooled for 4 polymorphisms: rs9332739 and rs547154 in the C2 gene and rs4151667 and rs641153 in the CFB gene. Data extraction and assessments for risk of bias were independently performed by 2 reviewers. Allele frequencies and allele and genotypic effects were pooled. Heterogeneity and publication bias were explored. Pooled minor allele frequencies for all 4 SNPs were between 4.7 and 9.6 for all polymorphisms, except for an Indian population in which the C allele at rs9332739 was the major allele. For the C2 polymorphisms, the minor C allele at rs9332739 and the minor T allele at rs547154 carried estimated relative risks (odds ratios) of 0.55 (95 confidence interval (CI): 0.46, 0.65) and 0.47 (95 CI: 0.39, 0.57), respectively. For the CFB polymorphisms, the minor A alleles at rs4151667 and rs614153 carried estimated risks of 0.54 (95 CI: 0.45, 0.64) and 0.41 (95 CI: 0.34, 0.51), respectively. These allele effects contributed to an absolute lowering of the risk of all AMD in Caucasian populations by 2.06.0. This meta-analysis provides a robust estimate of the protective association of C2/CFB with AMD. © 2012 The Author.
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    Causal Associations of Urate With Cardiovascular Risk Factors: Two-Sample Mendelian Randomization
    (2021-07-08) Thitiya Lukkunaprasit; Sasivimol Rattanasiri; Boonsong Ongphiphadhanakul; Gareth J. McKay; John Attia; Ammarin Thakkinstian; School of Medicine and Public Health; Rangsit University; Faculty of Medicine Ramathibodi Hospital, Mahidol University; School of Medicine, Dentistry and Biomedical Sciences
    Background: Mendelian Randomization (MR) studies show conflicting causal associations of genetically predicted serum urate with cardiovascular risk factors (i.e., hypertension, diabetes, lipid profile, and kidney function). This study aimed to robustly investigate a causal relationship between urate and cardiovascular risk factors considering single nucleotide polymorphisms (SNPs) as instrumental variables using two-sample MR and various sensitivity analyses. Methods: Data on SNP-urate associations were taken from the Global Urate Genetics Consortium and data on SNP-cardiovascular risk factor associations were taken from various consortia/UK Biobank. SNPs were selected by statistically and biologically driven approaches as instrumental variables. Various sensitivity analyses were performed using different MR methods including inverse variance weighted, MR-Egger, weighted median/mode, MR-PRESSO, and the contamination mixture method. Results: The statistically driven approach showed significant causal effects of urate on HDL-C and triglycerides using four of the six MR methods, i.e., every 1 mg/dl increase in genetically predicted urate was associated with 0.047 to 0.103 SD decrease in HDL-C and 0.034 to 0.207 SD increase in triglycerides. The biologically driven approach to selection of SNPs from ABCG2, SLC2A9, SLC17A1, SLC22A11, and SLC22A12 showed consistent causal effects of urate on HDL-C from all methods with 0.038 to 0.057 SD decrease in HDL-C per 1 mg/dl increase of urate, and no evidence of horizontal pleiotropy was detected. Conclusion: Our study suggests a significant and robust causal effect of genetically predicted urate on HDL-C. This finding may explain a small proportion (7%) of the association between increased urate and cardiovascular disease but points to urate being a novel cardiac risk factor.
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    The effects of vitamin E supplementation on malondialdehyde as a biomarker of oxidative stress in haemodialysis patients: a systematic review and meta-analysis
    (2021-12-01) Peter Bergin; Aoife Leggett; Chris R. Cardwell; Jayne V. Woodside; Ammarin Thakkinstian; Alexander P. Maxwell; Gareth J. McKay; Ramathibodi Hospital; Queen's University Belfast
    Background: Haemodialysis (HD) patients tend to have higher levels of oxidative stress (OS), associated with increased morbidity and premature mortality, compared to the general population. Levels of malondialdehyde (MDA), a biomarker of OS, are reduced by the antioxidant properties of vitamin E (VE) but outcomes from randomised control trials of VE supplementation on MDA in HD patients have been inconsistent. Methods: We undertook a systematic review and meta-analysis of adult HD patients from VE supplementation studies with measures of MDA. The following search criteria of MEDLINE and EMBASE were considered from inception to January 2020: ‘dialysis’ AND ‘Vitamin E OR tocopherol’ AND ‘malondialdehyde OR MDA’. Two reviewers independently extracted study data and assessed risk of bias. Mean MDA levels and standard deviation were determined before and after VE supplementation. Standardised mean difference (SMD) and standard error were calculated as the within person difference and units of measure were not consistently recorded across all studies. The SMD were pooled using random effects meta-analysis. Results: The SMD of MDA levels from 18 comparisons was significantly lower in HD patients following VE supplementation (− 1.55; confidence interval: − 2.17 to − 0.94, P < 0.00001). There were significant levels of heterogeneity between studies (I2 value = 91%; P < 0.00001) with evidence of potential publication bias toward smaller studies. Conclusions: Our findings support the use of VE to reduce the effects of OS in HD patients although high levels of heterogeneity and variation in the methodological approaches used by some studies highlight the need for further investigation.
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    Five authors reply
    (2013-05-01) Ammarin Thakkinstian; Gareth J. McKay; Julie Silvestri; Usha Chakravarthy; John Attia; Mahidol University; Queen's University Belfast; University of Newcastle, Australia
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    Prevention of venous thromboembolism in gynecological cancer patients undergoing major abdominopelvic surgery: A systematic review and network meta-analysis
    (2021-04-01) Putsarat Insin; Kasidin Vitoopinyoparb; Kunlawat Thadanipon; Chuenkamon Charakorn; John Attia; Gareth J. McKay; Ammarin Thakkinstian; School of Medicine and Public Health; Queen's University Belfast; Faculty of Medicine Ramathibodi Hospital, Mahidol University; Rajavithi Hospital
    Objective: Although thromboprophylaxis is recommended to reduce death and disability from venous thromboembolism (VTE), it remains underused due to a perceived risk of bleeding, especially in major abdominopelvic surgical patients. Methods: We conducted a systematic literature review to identify all eligible randomized controlled trials (RCTs), searching MEDLINE and Scopus databases through November 25, 2020. RCTs published in any language were eligible if they studied in gynecological cancer patients undergoing major abdominopelvic surgery and assessed efficacy of mechanical and pharmacological interventions. Studies with insufficient data for pooling or those comparing different doses/schedules of interventions were excluded. Outcomes of interest were composite VTE (ie, deep vein thrombosis or pulmonary embolism) and major bleeding. Relevant data were extracted for direct and network meta-analyses. Risk ratios (RR) and 95% confidence interval (CI) were estimated and the best intervention probability calculated for each outcome. This study was registered with PROSPERO (CRD42019145508). Results: We identified 1990 studies; 20 RCTs (4970 patients) were eligible. The overall risk of bias was of some concern. In direct meta-analyses, antithrombins were superior to unfractionated heparin in preventing composite VTE (RR 0.69; 95% CI 0.48–0.99), with no difference detected in the rate of major bleeding for any pairwise comparison. In network meta-analyses, graduated compression stockings plus low-molecular-weight heparin (LMWH) was top-ranked for prevention of composite VTE, whereas sequential compression devices (SCD) ranked second, after no treatment, for major bleeding. In a clustered ranking plot, SCD plus LMWH provided optimal balance between efficacy and safety. Conclusions: SCD plus LMWH might be safe and effective in VTE prevention following gynecological cancer surgery. However, the patient's bleeding risk should be considered to balance the risk and benefit of treatment.
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    Systematic review and meta-analysis of the association between complement component 3 and age-related macular degeneration: A HuGE review and meta-analysis
    (2011-06-15) Ammarin Thakkinstian; Gareth J. McKay; Mark McEvoy; Usha Chakravarthy; Subhabrata Chakrabarti; Giuliana Silvestri; Inderjeet Kaur; Xiaoxin Li; John Attia; Mahidol University; Queen's University Belfast; University of Newcastle, Australia; L.V. Prasad Eye Institute India; Peking University; Hunter Medical Research Institute, Australia; John Hunter Hospital
    The authors performed a meta-analysis to estimate the magnitude of polymorphism effects for the complement component C3 gene (C3) and their possible mode of action on age-related macular degeneration (AMD). The meta-analysis included 16 and 7 studies for rs2230199 and rs1047286, respectively. Data extraction and risk of bias assessments were performed in duplicate, and heterogeneity and publication bias were explored. There was moderate evidence for association between both polymorphisms and AMD in Caucasians. For rs2230199, patients with CG and GG genotypes were 1.44 (95% confidence interval (CI): 1.33, 1.56) and 1.88 (95% CI: 1.59, 2.23) times more likely to have AMD than patients with the CC genotype. For rs1047286, GA and AA genotypes had 1.27 (95% CI: 1.15, 1.41) and 1.70 (95% CI: 1.27, 2.11) times higher risk of AMD than did GG genotypes. These gene effects suggested an additive model. The population attributable risks for the GG/GC and AA/GA genotypes are approximately 5%-10%. Subgroup analysis by ethnicity indicates that these variants are very infrequent in Asians and that the observed gene effects are based largely on the high frequency within Caucasian populations. This meta-analysis supports the association between C3 and AMD and provides a robust estimate of the genetic risk. © 2011 The Author.