A common variant of NOS1AP is associated with QT interval duration in a Chinese population with Type 2 diabetes.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Lu
J
J
Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center of Diabetes, Shanghai, China.
Hu
C
C
Hu
W
W
Zhang
R
R
Wang
C
C
Qin
W
W
Yu
W
W
Xiang
K
K
Jia
W
W
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D044466:Asian People; D002317:Cardiovascular Agents / Q000627:therapeutic use; D016757:Death, Sudden, Cardiac / Q000453:epidemiology / Q000209:etiology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D003925:Diabetic Angiopathies / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008133:Long QT Syndrome / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D048868:Adaptor Proteins, Signal Transducing; D002317:Cardiovascular Agents; C488081:NOS1AP protein, human