Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine (originally named"Shanghai First People's Hospital"), Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, National Clinical Research Center for Eye Diseases, No.100 Haining Road, Shanghai, 20080, China.
Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, 200030, China.
BMC Med Genet. 2020 Feb 6;21(1):25. doi: 10.1186/s12881-020-0956-y.
The aim of this study was to explore the association between diabetic retinopathy (DR) and the variants of uncoupling proteins (UCPs) genes in a Chinese population of type 2 diabetes, in total and in patients of different glycemic status separately.
This case-control study included a total of 3107 participants from two datasets, among which 662 were DR patients (21.31%). Eighteen tag single nucleotide polymorphisms (SNPs) of UCP1, UCP2, and UCP3 were selected as genetic markers. TaqMan probes, Sequenom MassARRAY MALDI-TOF mass spectrometry platform and Affymetrix Genome-Wide Human SNP Array were used for genotyping. Online SHEsis software was used for association analysis. Bonferroni correction was used for multiple comparisons correction.
Three SNPs of UCP1: rs7688743 (A allele, OR = 1.192, p = 0.013), rs3811787 (T allele, OR = 0.863, p = 0.023), and rs10011540 (G allele, OR = 1.368, p = 0.004) showed association with DR after the adjustment of glucose, but only rs10011540 was marginally significantly associated with DR when Bonferroni correction was strictly applied (p = 0.048). In patients with uncontrolled glucose, rs7688743 (A allele, p = 0.012, OR = 1.309), rs10011540 (G allele, p = 0.033, OR = 1.432), and rs3811787 (T allele, p = 0.022, OR = 0.811) were associated with DR, while in participants with well controlled glucose, the rs2734827 of UCP3 was associated with DR (A allele, p = 0.017, OR = 0.532). Rs3811787 of UCP1 showed a protective effect to sight threatening DR (T allele, p = 0.007, OR = 0.490), and the association existed after the adjustment for environmental factors and the correction. In patients with uncontrolled glucose, the rs3811787 of UCP1 (T allele, p = 0.017, OR = 0.467) and the rs591758 of UCP3 (C allele, p = 0.026, OR = 0.103) were associated with STDR. While in those with well controlled glucose, only the rs7688743 of UCP1 showed a protective effect (A allele, p = 0.024, OR = 0.049). None of the associations remain significant when Bonferroni correction was strictly applied (all p < 0.05).
The rs10011540 and rs3811787 of the UCP1 gene was marginally significantly associated with DR in Chinese type 2 diabetes patients. There might be different mechanisms of DR development in patients with different glycemic status.
本研究旨在探讨在中国 2 型糖尿病人群中，解偶联蛋白（UCP）基因的变异与糖尿病视网膜病变（DR）之间的关联，包括总体人群和不同血糖状态的患者。
本病例对照研究共纳入来自两个数据集的 3107 名参与者，其中 662 名为 DR 患者（21.31%）。选择了 UCP1、UCP2 和 UCP3 的 18 个标签单核苷酸多态性（SNP）作为遗传标记。使用 TaqMan 探针、Sequenom MassARRAY MALDI-TOF 质谱平台和 Affymetrix 全基因组人类 SNP 芯片进行基因分型。使用在线 SHEsis 软件进行关联分析。使用 Bonferroni 校正进行多重比较校正。
UCP1 的三个 SNP：rs7688743（A 等位基因，OR=1.192，p=0.013）、rs3811787（T 等位基因，OR=0.863，p=0.023）和 rs10011540（G 等位基因，OR=1.368，p=0.004）在葡萄糖调整后与 DR 相关，但仅 rs10011540 在严格应用 Bonferroni 校正时与 DR 具有边缘显著相关性（p=0.048）。在血糖控制不佳的患者中，rs7688743（A 等位基因，p=0.012，OR=1.309）、rs10011540（G 等位基因，p=0.033，OR=1.432）和 rs3811787（T 等位基因，p=0.022，OR=0.811）与 DR 相关，而在血糖控制良好的患者中，UCP3 的 rs2734827 与 DR 相关（A 等位基因，p=0.017，OR=0.532）。UCP1 的 rs3811787 对威胁视力的 DR 具有保护作用（T 等位基因，p=0.007，OR=0.490），并且在调整环境因素和校正后仍然存在关联。在血糖控制不佳的患者中，UCP1 的 rs3811787（T 等位基因，p=0.017，OR=0.467）和 UCP3 的 rs591758（C 等位基因，p=0.026，OR=0.103）与 STDR 相关。而在血糖控制良好的患者中，只有 UCP1 的 rs7688743 具有保护作用（A 等位基因，p=0.024，OR=0.049）。当严格应用 Bonferroni 校正时，所有关联均不再显著（均 p<0.05）。
UCP1 基因的 rs10011540 和 rs3811787 与中国 2 型糖尿病患者的 DR 具有边缘显著相关性。不同血糖状态的患者中，DR 的发展机制可能不同。
