内皮型一氧化氮合酶基因多态性与2型糖尿病并发勃起功能障碍的相关性研究

Association between polymorphism of endothelial nitric oxide synthase gene and type 2 diabetic patients with erectile dysfunction

目的探讨内皮型一氧化氮合酶(ecNOS)基因内含子4可变数目串联重复序列(4VNTR)插入/缺失多态性(4b/a)和外显子7单核苷酸多态性(G894T)与男性2型糖尿病(T2DM)并发勃起功能障碍(DED)的关联性。方法提取108例男性T2DM患者、94例DED患者及100例男性健康人(NC)的基因组DNA,用聚合酶链反应-可变数目串联重复序列法(PCR)测定4VNTR多态性;聚合酶链反应-限制片段长度多态性法(PCR-RFLP)测定G894T多态性。结果DED组吸烟史、糖尿病周围血管病变(DPA)均高于T2DM组(P<0.01);NC组、T2DM组、DED组3组低密度脂蛋白胆固醇(LDL-C)分别为(2.37±0.86)mmol/L、(2.85±0.74)mmol/L、(3.12±0.92)mmol/L,糖化血红蛋白(HbA1c)分别为(6.40±0.64)%、(5.06±1.09)%、(7.32±0.66)%(P<0.05或<0.01);T2DM组、DED组甘油三酯(TG)和总胆固醇(TC)均高于NC组,TG为(1.76±0.66)mmol/L、(1.89±0.52)mmol/Lvs(1.35±0.54)mmol/L,TC为(4.95±0.77)mmol/L、(5.06±1.09)mmol/Lvs(4.31±0.86)mmol/L(均P<0.01);NC组、T2DM组、DED组3组间4VNTR多态性基因型(χ2=7.142,P=0.028)、等位基因(χ2=9.929,P=0.007)和G894T多态性基因型(χ2=2.118,P=0.002)、等位基因(χ2=15.468,P=0.000)频率分布差异均有统计学意义。logistic回归分析显示携带ecNOS4a等位基因(OR=2.282,P=0.012)、T等位基因(OR=5.217,P=0.002)以及合并DPA(OR=3.958,P=0.006)的T2DM患者并发DED的危险性更高。结论携带ecNOS基因内含子4a等位基因、894位点T等位基因以及合并DPA是男性T2DM并发DED的独立危险因素。

Objective To investigate the relationship between the insert/deletion polymorphism of variable number of tandem repeat in intron 4（4b/a） or the single nucleotide polymorphism in exon 7 （G894T） of endothelial nitric oxide synthase（ecNOS） gene and type 2 diabetic patients with erectile dysfunction. Methods In 108 patients with type 2 diabetes mellitus（T2DM）, 94 T2DM patients with diabetic erectile dysfunction（DED） and 100 healthy controls（NC） ,the polymorphism of 4VNTR was determined by polymerase chain reaction-variable number of tandem repeat analysis （PCR）, and the polymorphism of G894T was determined by polymerase chain reaction-restriction fragment length polymorphism analysis（PCR-RFLP）. Results Smoking history and diabetic peripheral arterial disease （DPA） in DED group were higher than those of T2DM group（ P d0.01）. The concentration of LDL-C increased from NC group,T2DM group and DED group, repectively （2.37±0.86） mmol/L vs （2.85 ± 0.74） mmol/L vs （3.12 ± 0.92） mmol/L （ P 〈0.05 or 〈0.01）. And the concentration of HbA1 c increased from NC group, T2DM group and DED group （6.40 ± 0.64）% vs （5.06 ± 1.09）% vs （7.32 ± 0.66）% （ P 〈0.05 or 〈0.01）. The concentrations of TG in T2DM and DED group were higher than that of NC group, repectively （1.76 ± 0.66） mmol/L, （1.89 ± 0.52） mmol/L vs （1.35±0.54） mmol/L （ P 〈0.01） ,and the concentration of TC in T2DM and DED group was higher than that of NC group,repectively （4.95 ±0.77） mmol/L, （5.06±1.09） mmol/L vs （4.31 ±0.86） mmol/L （all P〈 0. 01）. The frequencies of allele 4a, genotype containing with allele 4a （4b/a or 4a） and the frequencies of allele T, genotype containing with allele T（GT or TT） in DED group were significantly higher than those in DM group or NC group （all P 〈0.01）. Logistic regression analysis showed that carriers of allele 4a, allele T of ecNOS gene and DPA had a greater risk of diabetic erectile dysfunction. Conclusion The allele 4a, allele T of ecNOS gene and DPA are independent risk factors of T2DM patients with DED.