Sesti Luís F C, Crispim Daisy, Canani Luís H, Polina Evelise R, Rheinheimer Jakeline, Carvalho Patrícia S, Gross Jorge L, Santos Kátia G
Laboratory of Human Molecular Genetics, Universidade Luterana do Brasil (ULBRA), Canoas, Brazil.
Endocrine Division, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.
Invest Ophthalmol Vis Sci. 2015 Jan 29;56(2):1184-90. doi: 10.1167/iovs.14-15758.
We tested the hypothesis that tumor necrosis factor (TNF) gene polymorphisms are associated with diabetic retinopathy (DR) in Caucasians with type 2 diabetes mellitus.
In a case-control study, the -238G>A (rs361525), -308G>A (rs1800629), and -857C>T (rs1799724) polymorphisms of the TNF gene were genotyped in 745 outpatients with type 2 diabetes, including 331 subjects without DR, 246 with nonproliferative DR (NPDR), and 168 with proliferative DR (PDR).
Genotype and allele frequencies of the -238G>A, -308G>A, and -857C>T polymorphisms in subjects with NPDR were not significantly different from those of subjects without DR (P > 0.05 for all comparisons). However, the A allele of the -308G>A polymorphism was more frequent in subjects with PDR than in those with no DR (18.1% vs. 11.5%, corrected P = 0.035). Multivariate logistic regression analysis showed that the -308A allele was independently associated with an increased risk of PDR, under a dominant model (adjusted odds ratio [aOR], 1.82; 95% confidence interval [CI], 1.11-2.98). The combined analysis of the three polymorphisms also showed that haplotypes containing the -308A allele were associated with an increased risk of PDR (aOR, 2.36; 95% CI, 1.29-4.32).
This study detected, for the first time to our knowledge, an independent association of the -308G>A polymorphism in the TNF gene with PDR in Caucasian Brazilians with type 2 diabetes. This finding suggests that TNF is a potential susceptibility gene for PDR.
我们检验了肿瘤坏死因子（TNF）基因多态性与2型糖尿病白种人糖尿病视网膜病变（DR）相关的假设。
在一项病例对照研究中，对745例2型糖尿病门诊患者的TNF基因-238G>A（rs361525）、-308G>A（rs1800629）和-857C>T（rs1799724）多态性进行基因分型，其中包括331例无DR患者、246例非增殖性DR（NPDR）患者和168例增殖性DR（PDR）患者。
NPDR患者中-238G>A、-308G>A和-857C>T多态性的基因型和等位基因频率与无DR患者相比无显著差异（所有比较P>0.05）。然而，-308G>A多态性的A等位基因在PDR患者中比在无DR患者中更常见（18.1%对11.5%，校正P=0.035）。多因素逻辑回归分析显示，在显性模型下，-308A等位基因与PDR风险增加独立相关（调整后的优势比[aOR]，1.82；95%置信区间[CI]，1.11-2.98）。对这三种多态性的联合分析还显示，含有-308A等位基因的单倍型与PDR风险增加相关（aOR，2.36；95%CI，1.29-4.32）。
据我们所知，本研究首次检测到巴西白种人2型糖尿病患者中TNF基因-308G>A多态性与PDR存在独立关联。这一发现表明TNF是PDR的一个潜在易感基因。
