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Association analysis of nine candidate gene polymorphisms in Indian patients with type 2 diabetic retinopathy
BACKGROUND: Diabetic 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 t...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2010
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2994838/ https://www.ncbi.nlm.nih.gov/pubmed/21067572 http://dx.doi.org/10.1186/1471-2350-11-158 |
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author | Balasubbu, Suganthalakshmi Sundaresan, Periasamy Rajendran, Anand Ramasamy, Kim Govindarajan, Gowthaman Perumalsamy, Namperumalsamy Hejtmancik, J Fielding |
author_facet | Balasubbu, Suganthalakshmi Sundaresan, Periasamy Rajendran, Anand Ramasamy, Kim Govindarajan, Gowthaman Perumalsamy, Namperumalsamy Hejtmancik, J Fielding |
author_sort | Balasubbu, Suganthalakshmi |
collection | PubMed |
description | BACKGROUND: Diabetic 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). METHODS: Seven 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. RESULTS: Among 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. CONCLUSIONS: This study confirms significant association of one polymorphism only (rs2070600 in RAGE) with DR in an Indian population which had T2DM. |
format | Text |
id | pubmed-2994838 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-29948382010-12-01 Association analysis of nine candidate gene polymorphisms in Indian patients with type 2 diabetic retinopathy Balasubbu, Suganthalakshmi Sundaresan, Periasamy Rajendran, Anand Ramasamy, Kim Govindarajan, Gowthaman Perumalsamy, Namperumalsamy Hejtmancik, J Fielding BMC Med Genet Research Article BACKGROUND: Diabetic 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). METHODS: Seven 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. RESULTS: Among 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. CONCLUSIONS: This study confirms significant association of one polymorphism only (rs2070600 in RAGE) with DR in an Indian population which had T2DM. BioMed Central 2010-11-10 /pmc/articles/PMC2994838/ /pubmed/21067572 http://dx.doi.org/10.1186/1471-2350-11-158 Text en Copyright ©2010 Balasubbu et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 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. |
spellingShingle | Research Article Balasubbu, Suganthalakshmi Sundaresan, Periasamy Rajendran, Anand Ramasamy, Kim Govindarajan, Gowthaman Perumalsamy, Namperumalsamy Hejtmancik, J Fielding Association analysis of nine candidate gene polymorphisms in Indian patients with type 2 diabetic retinopathy |
title | Association analysis of nine candidate gene polymorphisms in Indian patients with type 2 diabetic retinopathy |
title_full | Association analysis of nine candidate gene polymorphisms in Indian patients with type 2 diabetic retinopathy |
title_fullStr | Association analysis of nine candidate gene polymorphisms in Indian patients with type 2 diabetic retinopathy |
title_full_unstemmed | Association analysis of nine candidate gene polymorphisms in Indian patients with type 2 diabetic retinopathy |
title_short | Association analysis of nine candidate gene polymorphisms in Indian patients with type 2 diabetic retinopathy |
title_sort | association analysis of nine candidate gene polymorphisms in indian patients with type 2 diabetic retinopathy |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2994838/ https://www.ncbi.nlm.nih.gov/pubmed/21067572 http://dx.doi.org/10.1186/1471-2350-11-158 |
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