Relationship between genetic variants in myocardial sodium and potassium channel genes and QT interval duration in diabetics: the Diabetes Heart Study.

Lehtinen AB, Daniel KR, Shah SA, Nelson MR, Ziegler JT, Freedman BI, Carr JJ, Herrington DM, Langefeld CD, Bowden DW
Ann Noninvasive Electrocardiol. 2009 14 (1): 72-9

PMID: 19149796 · PMCID: PMC3650725 · DOI:10.1111/j.1542-474X.2008.00276.x

BACKGROUND - 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.

METHODS - 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.

RESULTS - 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.

CONCLUSIONS - 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.

MeSH Terms (24)

Aged Alleles Analysis of Variance Cohort Studies Comorbidity Diabetes Mellitus, Type 2 Electrocardiography Female Genetic Predisposition to Disease Genetic Variation Genotype Humans KCNQ1 Potassium Channel KCNQ2 Potassium Channel Long QT Syndrome Male Middle Aged Muscle Proteins NAV1.5 Voltage-Gated Sodium Channel Polymorphism, Single Nucleotide Probability Prognosis Risk Assessment Sodium Channels

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