Association analysis of nine candidate gene polymorphisms in Indian patients with type 2 diabetic retinopathy

BMC Medical Genetics

Research Article

Gowthaman Govindarajan¹  Periasamy Sundaresan¹  Suganthalakshmi Balasubbu²  J Fielding Hejtmancik³  Kim Ramasamy⁴  Namperumalsamy Perumalsamy⁴  Anand Rajendran⁴ 

[1] Aravind Medical Research Foundation, Dr. G. Venkataswamy Eye Research Institute, Aravind Eye Hospital, #1, Anna Nagar, 625 020, Madurai, India;Aravind Medical Research Foundation, Dr. G. Venkataswamy Eye Research Institute, Aravind Eye Hospital, #1, Anna Nagar, 625 020, Madurai, India;Ophthalmic Genetics and Visual Function Branch, National Eye Institute, NIH, Bethesda, MD, USA;Ophthalmic Genetics and Visual Function Branch, National Eye Institute, NIH, Bethesda, MD, USA;Ophthalmic Genetics and Visual Function Branch, National Eye Institute, NIH, 5635 Fisher's Lane, 20852, Rockville, MD, USA;Retina Clinic, Aravind Eye Hospital, #1, Anna Nagar, 625 020, Madurai, India;

关键词: Diabetic Retinopathy;    Proliferative Diabetic Retinopathy;    Pigment Epithelium Derive Factor;    Random Blood Sugar;    Dinucleotide Repeat Polymorphism;   

DOI  :  10.1186/1471-2350-11-158

 received in 2010-03-20, accepted in 2010-11-10,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundDiabetic retinopathy (DR) is classically defined as a microvasculopathy that primarily affects the small blood vessels of the inner retina as a complication of diabetes mellitus (DM).It is a multifactorial disease with a strong genetic component. The aim of this study is to investigate the association of a set of nine candidate genes with the development of diabetic retinopathy in a South Indian cohort who have type 2 diabetes mellitus (T2DM).MethodsSeven candidate genes (RAGE, PEDF, AKR1B1, EPO, HTRA1, ICAM and HFE) were chosen based on reported association with DR in the literature. Two more, CFH and ARMS2, were chosen based on their roles in biological pathways previously implicated in DR. Fourteen single nucleotide polymorphisms (SNPs) and one dinucleotide repeat polymorphism, previously reported to show association with DR or other related diseases, were genotyped in 345 DR and 356 diabetic patients without retinopathy (DNR). The genes which showed positive association in this screening set were tested further in additional sets of 100 DR and 90 DNR additional patients from the Aravind Eye Hospital. Those which showed association in the secondary screen were subjected to a combined analysis with the 100 DR and 100 DNR subjects previously recruited and genotyped through the Sankara Nethralaya Hospital, India. Genotypes were evaluated using a combination of direct sequencing, TaqMan SNP genotyping, RFLP analysis, and SNaPshot PCR assays. Chi-square and Fisher exact tests were used to analyze the genotype and allele frequencies.ResultsAmong the nine loci (15 polymorphisms) screened, SNP rs2070600 (G82S) in the RAGE gene, showed significant association with DR (allelic P = 0.016, dominant model P = 0.012), compared to DNR. SNP rs2070600 further showed significant association with DR in the confirmation cohort (P = 0.035, dominant model P = 0.032). Combining the two cohorts gave an allelic P < 0.003 and dominant P = 0.0013). Combined analysis with the Sankara Nethralaya cohort gave an allelic P = 0.0003 and dominant P = 0.00011 with an OR = 0.49 (0.34 - 0.70) for the minor allele. In HTRA1, rs11200638 (G>A), showed marginal significance with DR (P = 0.055) while rs10490924 in LOC387715 gave a P = 0.07. No statistical significance was observed for SNPs in the other 7 genes studied.ConclusionsThis study confirms significant association of one polymorphism only (rs2070600 in RAGE) with DR in an Indian population which had T2DM.

【 授权许可】

Unknown   
© Balasubbu et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.