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Article: Impact of genetic loci identified in genome-wide association studies on diabetic retinopathy in Chinese patients with type 2 diabetes

TitleImpact of genetic loci identified in genome-wide association studies on diabetic retinopathy in Chinese patients with type 2 diabetes
Authors
KeywordsSight-threatening diabetic retinopathy
Proliferative diabetic retinopathy
INSR
Genome-wide association studies
Genetic variants
Diabetic retinopathy
Issue Date2016
Citation
Investigative Ophthalmology and Visual Science, 2016, v. 57, n. 13, p. 5518-5524 How to Cite?
Abstract© 2016, Association for Research in Vision and Ophthalmology Inc. All rights reserved.PURPOSE. Diabetic retinopathy (DR) is a common microvascular complication of type 2 diabetes (T2DM). Genome-wide association studies (GWAS) had identified novel DRsusceptibility genetic variants in various populations. We examined the associations of these DR-associated single nucleotide polymorphisms (SNPs) with severe DR in a Chinese T2DM cohort. METHODS. Cross-sectional case-control studies on sight-threatening DR (STDR) and proliferative DR (PDR) were performed. We genotyped 38 SNPs showing top association signals with DR in previous GWAS in 567 STDR cases, including 309 with PDR and 1490 non-DR controls. Multiple logistic regression models with adjustment for conventional risk factors, including age, sex, duration of diabetes, and presence of hypertension, were employed. RESULTS. The strongest association was found at INSR rs2115386, an intronic SNP of INSR: Padjusted = 9.13 × 10-4 (odds ratio [OR],1.28; 95% confidence interval [95%CI], 1.11-1.48) for STDR, and Padjusted = 1.12 × 10-4 (OR [95%CI],1.44 [1.20-1.74]) for PDR. rs599019 located downstream of COLEC12 (Padjusted = 0.019; OR [95%CI],1.19 [1.03-1.38]) and rs4462262 located at an intergenic region between ZWINT and MRPS35P3 (Padjusted = 0.041; OR [95%CI],1.38[1.01-1.89]) also were significantly associated with STDR, but not with PDR alone. On the other hand, MYT1L-LOC729897 rs10199521 (Padjusted = 0.022; OR [95%CI],1.25 [1.03-1.51]) and API5 rs899036 (Padjusted = 0.049; OR [95%CI],1.36 [1.00-1.85]) showed significant independent associations only with PDR. Similar results were obtained when hemoglobin A1c also was included in the adjustment models. CONCLUSIONS. We demonstrated the significant and independent associations of several GWAS-identified SNPs with DR in Chinese T2DM patients with severe DR. The findings on INSR rs2115386 are supportive of the role of insulin resistance, or the compensatory hyperinsulinemia, in the pathogenesis of DR.
Persistent Identifierhttp://hdl.handle.net/10722/238164
ISSN
2023 Impact Factor: 5.0
2023 SCImago Journal Rankings: 1.422
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorCheung, Chloe Y Y-
dc.contributor.authorHui, Elaine Y L-
dc.contributor.authorLee, Chi Ho-
dc.contributor.authorKwok, Kelvin H M-
dc.contributor.authorGangwani, Rita A.-
dc.contributor.authorLi, Kenneth K W-
dc.contributor.authorChan, Jeffrey C W-
dc.contributor.authorWoo, Yu Cho-
dc.contributor.authorChow, Wing Sun-
dc.contributor.authorYuen, Michele M A-
dc.contributor.authorWong, Rachel L C-
dc.contributor.authorFong, Carol H Y-
dc.contributor.authorXu, Aimin-
dc.contributor.authorWong, David S H-
dc.contributor.authorSham, Pak Chung-
dc.contributor.authorLam, Karen S L-
dc.date.accessioned2017-02-03T02:13:14Z-
dc.date.available2017-02-03T02:13:14Z-
dc.date.issued2016-
dc.identifier.citationInvestigative Ophthalmology and Visual Science, 2016, v. 57, n. 13, p. 5518-5524-
dc.identifier.issn0146-0404-
dc.identifier.urihttp://hdl.handle.net/10722/238164-
dc.description.abstract© 2016, Association for Research in Vision and Ophthalmology Inc. All rights reserved.PURPOSE. Diabetic retinopathy (DR) is a common microvascular complication of type 2 diabetes (T2DM). Genome-wide association studies (GWAS) had identified novel DRsusceptibility genetic variants in various populations. We examined the associations of these DR-associated single nucleotide polymorphisms (SNPs) with severe DR in a Chinese T2DM cohort. METHODS. Cross-sectional case-control studies on sight-threatening DR (STDR) and proliferative DR (PDR) were performed. We genotyped 38 SNPs showing top association signals with DR in previous GWAS in 567 STDR cases, including 309 with PDR and 1490 non-DR controls. Multiple logistic regression models with adjustment for conventional risk factors, including age, sex, duration of diabetes, and presence of hypertension, were employed. RESULTS. The strongest association was found at INSR rs2115386, an intronic SNP of INSR: Padjusted = 9.13 × 10-4 (odds ratio [OR],1.28; 95% confidence interval [95%CI], 1.11-1.48) for STDR, and Padjusted = 1.12 × 10-4 (OR [95%CI],1.44 [1.20-1.74]) for PDR. rs599019 located downstream of COLEC12 (Padjusted = 0.019; OR [95%CI],1.19 [1.03-1.38]) and rs4462262 located at an intergenic region between ZWINT and MRPS35P3 (Padjusted = 0.041; OR [95%CI],1.38[1.01-1.89]) also were significantly associated with STDR, but not with PDR alone. On the other hand, MYT1L-LOC729897 rs10199521 (Padjusted = 0.022; OR [95%CI],1.25 [1.03-1.51]) and API5 rs899036 (Padjusted = 0.049; OR [95%CI],1.36 [1.00-1.85]) showed significant independent associations only with PDR. Similar results were obtained when hemoglobin A1c also was included in the adjustment models. CONCLUSIONS. We demonstrated the significant and independent associations of several GWAS-identified SNPs with DR in Chinese T2DM patients with severe DR. The findings on INSR rs2115386 are supportive of the role of insulin resistance, or the compensatory hyperinsulinemia, in the pathogenesis of DR.-
dc.languageeng-
dc.relation.ispartofInvestigative Ophthalmology and Visual Science-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectSight-threatening diabetic retinopathy-
dc.subjectProliferative diabetic retinopathy-
dc.subjectINSR-
dc.subjectGenome-wide association studies-
dc.subjectGenetic variants-
dc.subjectDiabetic retinopathy-
dc.titleImpact of genetic loci identified in genome-wide association studies on diabetic retinopathy in Chinese patients with type 2 diabetes-
dc.typeArticle-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1167/iovs.16-20094-
dc.identifier.scopuseid_2-s2.0-84992365643-
dc.identifier.hkuros272185-
dc.identifier.volume57-
dc.identifier.issue13-
dc.identifier.spage5518-
dc.identifier.epage5524-
dc.identifier.eissn1552-5783-
dc.identifier.isiWOS:000392469600059-
dc.identifier.issnl0146-0404-

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