Ling Wu1, Chi Chiu Wang1,2,3. 1. Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong, Hong Kong. 2. Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong. 3. School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong.
Abstract
BACKGROUND: Promoter plays important roles in regulating transcription of genes. Association studies of genetic variants in promoter region with type 2 diabetes (T2D) risk have been reported, but most were limited to small number of individual genetic variants and insufficient sample sizes. In addition, the effect of study populations and demographic characteristics were often neglected. METHODS: In this study, we conducted a large-scale meta-analysis and subgroup analysis of T2D associated genetic variants in the promoter regions to evaluate their contribution to the susceptibility in T2D. Alleles and genotypes from cohort or case-controlled studies were extracted for future study. Total 41 742 cases and 50 493 controls for three loci were involved in 70 articles. RESULTS: Seventy case-controlled studies of three genes with 41 742 cases and 50 493 controls were included. Meta-analysis showed only rs266729 and rs17300539 of ADIPOQ, and rs1884613, rs2144908, and rs4810424 of HNF4A were significantly associated with T2D risk. Subgroup analysis showed that both rs266729 and rs17300539 of ADIPOQ were associated with the risk of T2D in Caucasian population, but only rs266729 of ADIPOQ in Asian population and rs2144908 in other population including multinational North American. For diagnostic criteria, rs266729 of ADIPOQ and rs2144908 of HNF4A were associated with T2D risk when WHO/ADA diagnostic criteria were used. For genotyping methods, both rs266729 of ADIPOQ and rs2144908 of HNF4A were associated with T2D risk when other than Taqman and Sequencing methods were used. CONCLUSIONS: T2D was significantly associated with promoter rs266729, rs17300539, rs1884613, rs2144908, and rs4810424, and the association of T2D risk were affected by study population, diagnostic criteria, and genotype methods.
BACKGROUND: Promoter plays important roles in regulating transcription of genes. Association studies of genetic variants in promoter region with type 2 diabetes (T2D) risk have been reported, but most were limited to small number of individual genetic variants and insufficient sample sizes. In addition, the effect of study populations and demographic characteristics were often neglected. METHODS: In this study, we conducted a large-scale meta-analysis and subgroup analysis of T2D associated genetic variants in the promoter regions to evaluate their contribution to the susceptibility in T2D. Alleles and genotypes from cohort or case-controlled studies were extracted for future study. Total 41 742 cases and 50 493 controls for three loci were involved in 70 articles. RESULTS: Seventy case-controlled studies of three genes with 41 742 cases and 50 493 controls were included. Meta-analysis showed only rs266729 and rs17300539 of ADIPOQ, and rs1884613, rs2144908, and rs4810424 of HNF4A were significantly associated with T2D risk. Subgroup analysis showed that both rs266729 and rs17300539 of ADIPOQ were associated with the risk of T2D in Caucasian population, but only rs266729 of ADIPOQ in Asian population and rs2144908 in other population including multinational North American. For diagnostic criteria, rs266729 of ADIPOQ and rs2144908 of HNF4A were associated with T2D risk when WHO/ADA diagnostic criteria were used. For genotyping methods, both rs266729 of ADIPOQ and rs2144908 of HNF4A were associated with T2D risk when other than Taqman and Sequencing methods were used. CONCLUSIONS: T2D was significantly associated with promoter rs266729, rs17300539, rs1884613, rs2144908, and rs4810424, and the association of T2D risk were affected by study population, diagnostic criteria, and genotype methods.