Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center of Diabetes, Shanghai, China.
Diabet Med. 2010 Sep;27(9):1074-9. doi: 10.1111/j.1464-5491.2010.03072.x.
Electrocardiographic ventricular repolarization QT parameters are independent risk factors for cardiovascular events and sudden cardiac death in diabetic patients. The aim of the study was to investigate the association of polymorphisms of the nitric oxide synthase 1 adaptor protein (NOS1AP) gene with QT interval in Chinese subjects with or without Type 2 diabetes.
Three single nucleotide polymorphisms (SNPs) (rs10494366, rs12143842 and rs12029454) were genotyped in 1240 Type 2 diabetic patients (631 men and 609 women) and 1196 normal controls (433 men and 763 women). Individuals with overt diseases other than diabetes were excluded. Heart-rate corrected QT interval (QTc) was determined by standard 12-lead ECG and Bazett formula. Sex-pooled analysis and sex-specific analysis for genotype-phenotype association were both conducted.
In the diabetic group, the rs12143842 T allele was associated with a 3.87-ms (P = 0.014, empirical P = 0.039) increase in QTc duration for each additional allele copy, while rs10494366 and rs12029454 exhibited no significant association with QTc. We found no evidence of association for the three SNPs in subjects with normal glucose regulation. No significant SNP-gender and -diabetes affection interaction was observed.
The genetic variant rs12143842 in NOS1AP is associated with QT interval duration in a Chinese population with Type 2 diabetes. Future studies in different populations are needed to validate this finding and to evaluate the impact of NOS1AP variants on cardiovascular events and sudden cardiac death in diabetic patients.
心电图心室复极 QT 参数是糖尿病患者心血管事件和心源性猝死的独立危险因素。本研究旨在探讨一氧化氮合酶 1 衔接蛋白（NOS1AP）基因多态性与中国 2 型糖尿病患者或无 2 型糖尿病患者 QT 间期的关系。
在 1240 例 2 型糖尿病患者（631 名男性和 609 名女性）和 1196 名正常对照者（433 名男性和 763 名女性）中，对 3 个单核苷酸多态性（SNP）（rs10494366、rs12143842 和 rs12029454）进行基因分型。排除除糖尿病以外有明显疾病的个体。通过标准 12 导联心电图和 Bazett 公式确定心率校正 QT 间期（QTc）。进行了基因型-表型关联的性别合并分析和性别特异性分析。
在糖尿病组中，rs12143842 T 等位基因与每个额外等位基因拷贝 QTc 持续时间增加 3.87ms（P=0.014，经验 P=0.039）相关，而 rs10494366 和 rs12029454 与 QTc 无显著相关性。在血糖正常调节的受试者中，我们没有发现这三个 SNP 与 QT 相关的证据。未观察到 SNP-性别和 -糖尿病影响的相互作用。
NOS1AP 中的遗传变异 rs12143842 与中国 2 型糖尿病患者的 QT 间期持续时间有关。需要在不同人群中进行进一步的研究来验证这一发现，并评估 NOS1AP 变异对糖尿病患者心血管事件和心源性猝死的影响。
