Santos Kátia G, Canani Luís H, Gross Jorge L, Tschiedel Balduíno, Souto Kátia E, Roisenberg Israel
Genetics Department, Federal University of Rio Grande do Sul, Porto Alegre, RS - Brazil.
J Nephrol. 2005 Nov-Dec;18(6):733-8.
In this case-control study, we investigated the possible involvement of the p22phox C242T polymorphism in the development and progression of diabetic nephropathy (DN) in 535 Caucasian Brazilians with type 2 diabetes. We also evaluated the effects of the interaction of the C242T polymorphism with smoking and hypercholesterolemia on the susceptibility to nephropathy.
Genotype analysis was performed using polymerase chain reaction (PCR) followed by digestion with restriction enzyme. Logistic regression analysis was used to control for independent risk factors associated with nephropathy.
The genotype frequencies in patients with overt DN (CC/CT/TT: 0.36/0.47/0.17) were not significantly different from those of diabetic individuals with normoalbuminuria (0.47/0.41/0.12) or microalbuminuria (0.42/0.48/0.10) (p=0.214). Likewise, there were no differences in the T allele frequency among patients with normoalbuminuria, microalbuminuria or overt DN (0.33, 0.34 and 0.40, respectively; p=0.111). However, the T allele was found to be more frequent among smokers with overt nephropathy (macroalbuminuria and/or in dialysis) than those who had normoalbuminuria (43 vs. 32%, p=0.045). The multiple logistic regression analysis confirmed that the CT+TT genotypes were independently associated with a higher risk of having overt nephropathy among smokers [odds ratio (OR)=6.76, 95% confidence interval (95% CI) 1.83-25.02].
Our study shows a gene-environment interaction associated with the increased risk of DN progression in Caucasian Brazilian smokers with type 2 diabetes. Further studies should be performed to clarify whether it exists, and to what extent there is a relationship between the p22phox C242T polymorphism and DN.
在这项病例对照研究中，我们调查了535名患有2型糖尿病的巴西白种人中，p22phox C242T基因多态性在糖尿病肾病（DN）发生和发展中的可能作用。我们还评估了C242T基因多态性与吸烟及高胆固醇血症的相互作用对肾病易感性的影响。
采用聚合酶链反应（PCR），随后用限制性酶消化进行基因型分析。使用逻辑回归分析来控制与肾病相关的独立危险因素。
显性DN患者的基因型频率（CC/CT/TT：0.36/0.47/0.17）与正常白蛋白尿的糖尿病个体（0.47/0.41/0.12）或微量白蛋白尿的糖尿病个体（0.42/0.48/0.10）相比，无显著差异（p = 0.214）。同样，正常白蛋白尿、微量白蛋白尿或显性DN患者的T等位基因频率也无差异（分别为0.33、0.34和0.40；p = 0.111）。然而，发现显性肾病（大量白蛋白尿和/或透析）吸烟者中的T等位基因频率高于正常白蛋白尿吸烟者（43%对32%，p = 0.045）。多因素逻辑回归分析证实，CT + TT基因型与吸烟者发生显性肾病的较高风险独立相关[比值比（OR）= 6.76，95%置信区间（95%CI）1.83 - 25.02]。
我们的研究表明，在患有2型糖尿病的巴西白种人吸烟者中，基因 - 环境相互作用与DN进展风险增加相关。应进行进一步研究以阐明其是否存在，以及p22phox C242T基因多态性与DN之间的关系程度。
