Increasing evidence suggests that endothelin and nitric oxide synthase genes and their products exert biological effects on the vasculature via the nitric oxide or endothelin pathway. The aim of the study was to evaluate the association of rs10507875 and rs869109213 (alone or in interaction) with diabetic retinopathy (DR) in subjects with type 2 diabetes mellitus (T2DM). We genotyped the single nucleotide polymorphism rs10507875 of the endothelin receptor B gene (EDNRB) and variable number tandem repeats rs869109213 of the nitric oxide synthase 3 gene (NOS3) in 270 Slovenian patients with DR and T2DM and 256 controls with T2DM without clinical signs of DR. The genotyping was performed using either real-time polymerase chain reaction (PCR) or standard PCR. We found a significant association between the genotypes of NOS3 rs869109213 polymorphism and the risk of DR in the co-dominant model (4a4b genotype; 1.99-fold increased risk [1.09-3.65]; 95% confidence interval [CI]; p = 0.02), co-dominant model (4a4a genotype; 4.16-fold increased risk [1.03-16.74]; 95% CI; p = 0.04), and dominant model (4a4a and 4a4b genotypes; 2.22-fold increased risk [1.26-3.92]; 95% CI; p = 0.01) compared to the 4b4b genotype. Moreover, the joint effect of the two polymorphisms on DR risk was greater than the individual effect of each polymorphism in the analyzed genetic models. Additionally, adjusted odds ratio showed an increased risk in dominant × dominant (4.15-fold [1.40-12.26]; 95% CI; p = 0.01) and recessive × dominant (2.24-fold [1.25-4.01]; 95% CI; p = 0.02) genotype combinations of the two polymorphisms. In conclusion, our results indicate that NOS3 rs869109213 polymorphism alone or in a combination with EDNRB rs10507875 polymorphism may be associated with DR in Slovenian patients with T2DM.

中文翻译：

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内皮素受体B基因（EDNRB）多态性rs10507875和一氧化氮合酶3基因（NOS3）多态性rs869109213在斯洛文尼亚2型糖尿病和糖尿病性视网膜病患者中的联合作用。

越来越多的证据表明，内皮素和一氧化氮合酶基因及其产物通过一氧化氮或内皮素途径对脉管系统产生生物学作用。该研究的目的是评估rs10507875和rs869109213（单独或相互作用）与2型糖尿病（T2DM）患者的糖尿病性视网膜病变（DR）的关联。我们对270例斯洛文尼亚DR和T2DM患者和256例没有DR临床症状的斯洛文尼亚患者进行了内皮素受体B基因（EDNRB）的单核苷酸多态性rs10507875和一氧化氮合酶3基因（NOS3）的可变数目串联重复rs869109213基因分型。使用实时聚合酶链反应（PCR）或标准PCR进行基因分型。我们在共显性模型中发现NOS3基因rs869109213多态性基因型与DR风险之间存在显着关联（4a4b基因型；风险增加1.99倍[1.09-3.65]； 95％置信区间[CI]； p = 0.02） ，共显性模型（4a4a基因型；风险增加4.16倍[1.03-16.74]； 95％CI； p = 0.04）和显性模型（4a4a和4a4b基因型；风险提高2.22倍[1.26-3.92]； 95） ％CI； p = 0.01）与4b4b基因型相比。而且，在所分析的遗传模型中，两种多态性对DR风险的联合效应大于每种多态性的个体效应。此外，调整后的优势比显示显性×显性（4.15倍[1.40-12.26]； 95％CI； p = 0.01）和隐性×显性（2.24倍[1.25-4.01]; 95％CI; p = 0.02）两个多态性的基因型组合。