Investigation
Associations of single nucleotide polymorphisms of UCP genes with diabetic retinopathy in Chinese Han population
Peiyao Jin, Zhiqiang Li, Xian Xu, Jiangnan He, Jianhua Chen, Xun Xu, Xuan Du, Xuelin Bai, Bo Zhang, Xiangui He, Lina Lu, Jianfeng Zhu, Yongyong Shi, Haidong Zou
Published 2017-08-10
Cite as Chin J Exp Ophthalmol, 2017, 35(8): 737-742. DOI: 10.3760/cma.j.issn.2095-0160.2017.08.015
Abstract
BackgroundResearches showed that elevatory blood glucose level results in long-term damage of cells and tissue, or metabolic memory phenomenon, and manipulation of hyperglycemic memory is a good approach in the prevention of diabetic complications.However, its mechanism is not clear.It is speculated that the pathogenesis of diabetic retinopathy (DR) in diabetic patients may be associated to related mechanisms.Uncoupling proteins (UCPs) can decrease the production of reactive oxygen species (ROS), which may be related to DR.
ObjectiveThis study was to explore the association between DR and the single nucleotide polymorphisms (SNPs) of UCP genes in Chinese Han population with type 2 diabetes.
MethodsA cross-sectional study was performed.This study was approved by Ethic Committee of Affiliated First Hospital of Shanghai Jiao Tong University and complied with Declaration of Helsinki, and written informed consent was obtained from each subject prior to any medical examination.One thousand eight hundreds and seventy-five patients with type 2 diabetes mellitus were enrolled in Xinjing district of Shanghai city by cluster sampling from November 2014 to January 2015.The demographic and medical baseline characteristics, ocular examination and laboratory tests were obtained and periphery blood of 2 ml was collected for extraction of DNA.Eight tag SNPs of UCP1, three tag SNPs of UCP2, and seven tag SNPs of UCP3 were selected as marker locus for the detection of genotype by Sequenom Mass ARRAY.Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry platform were used for genotyping.Hardy-Weinberg equilibrium (HWE) analysis, allele and genotype frequencies, haplotype analysis, and association tests for DR and SNPs were performed by SAS and SHEsis software.
ResultsA total of 530 DR patients were checked out from 1 875 subjects with type 2 diabetes mellitus, with the detection rate of 28.27%.rs660339 locu of UCP2 gene and rs1626521, rs668514 locus of UCP3 gene appeared to have low detectable rates, and the secondary allele base frequency of rs632862 in UCP2 gene was <0.01 and rs15763 of UCP3 gene was unmatched with HWE, therefore, these locus analysis was not included.In 13 SNPs locus included in the analysis, only 2 SNPs of UCP1 gene were related to DR.Compared with the non-diabetic retinopathy (NDR) patients, the G allele frequency of rs10011540 was increased (P=0.03, OR=1.31, 95% confidence interval[CI]=1.03-1.67, and T allele frequency of rs3811787 was decreased (P=0.04, OR=0.86, 95%CI= 0.75-0.99) in DR patients.Genotyping detection showed that the C/C and A/A frequencies of rs3811790 in UCP1 gene were significantly more and C/A frequency was less in DR patients than those in NDR patients (all at P<0.01). The logistic regression analysis indicated an association of SNPs of rs10011540 and rs3811787 with DR independent from glucose and disease duration.
ConclusionsThe SNPs of rs10011540 and rs3811787 locus in UCP1 gene are associated with DR in Chinese type 2 diabetes patients.
Key words:
Diabetes mellitus, type 2/complications; Diabetic retinopathy/genetics; Uncoupling proteins; Polymorphism, genetic; Alleles; Gene frequency; Odds ratio; Cross-sectional study; Chinese
Contributor Information
Peiyao Jin
Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai 200080, China
Zhiqiang Li
Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai 200030, China
Xian Xu
Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai 200080, China
Jiangnan He
Shanghai Eye Disease Prevention and Treatment Center, Shanghai 200040, China
Jianhua Chen
Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai 200030, China
Xun Xu
Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai 200080, China
Xuan Du
Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai 200080, China
Xuelin Bai
Xinjing Community Health Service Center, Shanghai 200335, China
Bo Zhang
Shanghai Eye Disease Prevention and Treatment Center, Shanghai 200040, China
Xiangui He
Shanghai Eye Disease Prevention and Treatment Center, Shanghai 200040, China
Lina Lu
Shanghai Eye Disease Prevention and Treatment Center, Shanghai 200040, China
Jianfeng Zhu
Shanghai Eye Disease Prevention and Treatment Center, Shanghai 200040, China
Yongyong Shi
Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai 200030, China
Haidong Zou
Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai 200080, China
Shanghai Eye Disease Prevention and Treatment Center, Shanghai 200040, China
