Lehtinen Allison B, Daniel Kurt R, Shah Sidharth A, Nelson Matthew R, Ziegler Julie T, Freedman Barry I, Carr J Jeffrey, Herrington David M, Langefeld Carl D, Bowden Donald W
Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
Ann Noninvasive Electrocardiol. 2009 Jan;14(1):72-9. doi: 10.1111/j.1542-474X.2008.00276.x.
Genetic variants in myocardial sodium and potassium channel genes are associated with prolonged QT interval and increased risk of sudden death. It is unclear whether these genetic variants remain relevant in subjects with underlying conditions such as diabetes that are associated with prolonged QT interval.
We tested single nucleotide polymorphisms (SNPs) in five candidate genes for association with QT interval in a family-based study of subjects with type 2 diabetes mellitus (T2DM). Thirty-six previously reported SNPs were genotyped in KCNQ1, HERG, SCN5A, KCNE1, and KCNE2 in 901 European Americans from 366 families. The heart rate-corrected (QTc) durations were determined using the Marquette 12SL program. Associations between the QTc interval and the genotypes were evaluated using SOLAR adjusting for age, gender, T2DM status, and body mass index.
Within KCNQ1 there was weak evidence for association between the minor allele of IVS12 +14T>C and increased QTc (P = 0.02). The minor allele of rs2236609 in KCNE1 trended toward significance with longer QTc (P = 0.06), while the minor allele of rs1805123 in HERG trended toward significance with shorter QTc (P = 0.07). However, no statistically significant associations were observed between the remaining SNPs and QTc variation.
We found weak evidence of association between three previously reported SNPs and QTc interval duration. While it appears as though genetic variants in previously identified candidate genes may be associated with QT duration in subjects with diabetes, the clinical implications of these associations in diabetic subjects at high risk for sudden death remain to be determined.
心肌钠通道和钾通道基因的遗传变异与QT间期延长及猝死风险增加相关。目前尚不清楚这些遗传变异在患有如糖尿病等与QT间期延长相关的基础疾病的患者中是否仍然具有相关性。
在一项基于家系的2型糖尿病（T2DM）患者研究中，我们检测了五个候选基因中的单核苷酸多态性（SNP）与QT间期的关联。对来自366个家庭的901名欧裔美国人的KCNQ1、HERG、SCN5A、KCNE1和KCNE2基因中的36个先前报道的SNP进行基因分型。使用Marquette 12SL程序确定心率校正后的（QTc）时长。使用SOLAR软件对年龄、性别、T2DM状态和体重指数进行校正后，评估QTc间期与基因型之间的关联。
在KCNQ1基因中，IVS12 +14T>C的次要等位基因与QTc增加之间存在微弱的关联证据（P = 0.02）。KCNE1基因中rs2236609的次要等位基因与较长的QTc呈显著趋势（P = 0.06），而HERG基因中rs1805123的次要等位基因与较短的QTc呈显著趋势（P = 0.07）。然而，在其余SNP与QTc变异之间未观察到统计学上的显著关联。
我们发现三个先前报道的SNP与QTc间期时长之间存在微弱的关联证据。虽然先前确定的候选基因中的遗传变异似乎可能与糖尿病患者的QT时长相关，但这些关联在猝死高危糖尿病患者中的临床意义仍有待确定。
