Ezzidi Intissar, Mtiraoui Nabil, Mohamed Manel Ben Hadj, Mahjoub Touhami, Kacem Maha, Almawi Wassim Y
Research Unit of Haematological and Autoimmune Diseases, Faculty of Pharmacy, Monastir, Center University, Tunisia.
Clin Endocrinol (Oxf). 2008 Apr;68(4):542-6. doi: 10.1111/j.1365-2265.2007.03089.x. Epub 2007 Oct 31.
The possible association between the endothelial nitric oxide (eNOS) gene T-786C (promoter region), 27-bp repeat 4b/4a (intron 4), and Glu298Asp (exon 7) polymorphisms with diabetic retinopathy (DR) was investigated.
A retrospective case-control study.
A total of 872 type 2 diabetes (T2DM) patients were studied, of whom 383 presented with preproliferative/proliferative retinopathy (DR group), and 489 with absent/mild retinopathy (DWR group).
Glu298Asp and T-786C genotyping was carried out by PCR-RFLP analysis, while 4b/4a was assessed by PCR. Genotype distribution was compared using the chi(2)-test, and the contributions of the polymorphisms to DR were analysed by haplotype analysis and multivariate regression analysis.
Lower prevalence of mutant 4a (P = 0.011), and heterozygous 4b/4a (P = 0.042) were seen in the DR compared to the DWR groups; the allele and genotype distribution of the Glu298Asp and T-786C polymorphisms were comparable between DR and DWR groups. Three-loci haplotype analysis demonstrated significant association between eNOS variants and DR, with protective [haplotype 122 (Glu298/4a/-786C)], and susceptible haplotypes [haplotypes 112 (Glu298/4b/-786C) and 222 (Asp298/4a/-786C)] identified. Multivariate regression analysis confirmed the association between haplotypes 122 (P = 0.015); 112 (P = 0.027), and 222 (P = 0.048) and DR, after controlling for potential covariates (including age, sex, age of disease onset; HbA1c; hypertension, total cholesterol).
This study identifies genetic variation at the eNOS locus as genetic risk factor for diabetic retinopathy, which may serve as a useful marker of increased susceptibility to the risk of retinopathy.
研究内皮型一氧化氮合酶（eNOS）基因T-786C（启动子区域）、27碱基重复序列4b/4a（第4内含子）和Glu298Asp（第7外显子）多态性与糖尿病视网膜病变（DR）之间可能存在的关联。
一项回顾性病例对照研究。
共研究了872例2型糖尿病（T2DM）患者，其中383例患有增殖前期/增殖性视网膜病变（DR组），489例无/轻度视网膜病变（糖尿病性视网膜病变未累及组，DWR组）。
采用聚合酶链反应-限制性片段长度多态性分析（PCR-RFLP）进行Glu298Asp和T-786C基因分型，通过聚合酶链反应（PCR）评估4b/4a。使用卡方检验比较基因型分布，并通过单倍型分析和多因素回归分析分析多态性对DR的影响。
与DWR组相比，DR组中突变型4a（P = 0.011）和杂合型4b/4a（P = 0.042）的患病率较低；DR组和DWR组之间Glu298Asp和T-786C多态性的等位基因和基因型分布相当。三位点单倍型分析表明eNOS变异与DR之间存在显著关联，确定了保护性单倍型[单倍型122（Glu298/4a/-786C）]和易感单倍型[单倍型112（Glu298/4b/-786C）和222（Asp298/4a/-786C）]。在控制潜在协变量（包括年龄、性别、发病年龄、糖化血红蛋白、高血压、总胆固醇）后，多因素回归分析证实单倍型122（P = 0.015）、112（P = 0.027）和222（P = 0.048）与DR之间存在关联。
本研究确定eNOS基因座的遗传变异是糖尿病视网膜病变的遗传危险因素，这可能是视网膜病变易感性增加的一个有用标志物。
