Faculty Collaboration Database

Genome-wide association study identifies single-nucleotide polymorphism in KCNB1 associated with left ventricular mass in humans: the HyperGEN Study. BMC Med Genet 2009 May 19;10:43

Date

05/21/2009

Pubmed ID

19454037

Pubmed Central ID

PMC2692849

DOI

10.1186/1471-2350-10-43

Scopus ID

2-s2.0-66649106445 (requires institutional sign-in at Scopus site)   40 Citations

Abstract

BACKGROUND: We conducted a genome-wide association study (GWAS) and validation study for left ventricular (LV) mass in the Family Blood Pressure Program-HyperGEN population. LV mass is a sensitive predictor of cardiovascular mortality and morbidity in all genders, races, and ages. Polymorphisms of candidate genes in diverse pathways have been associated with LV mass. However, subsequent studies have often failed to replicate these associations. Genome-wide association studies have unprecedented power to identify potential genes with modest effects on left LV mass. We describe here a GWAS for LV mass in Caucasians using the Affymetrix GeneChip Human Mapping 100 k Set. Cases (N = 101) and controls (N = 101) were selected from extreme tails of the LV mass index distribution from 906 individuals in the HyperGEN study. Eleven of 12 promising (Q < 0.8) single-nucleotide polymorphisms (SNPs) from the genome-wide study were successfully genotyped using quantitative real time PCR in a validation study.

RESULTS: Despite the relatively small sample, we identified 12 promising SNPs in the GWAS. Eleven SNPs were successfully genotyped in the validation study of 704 Caucasians and 1467 African Americans; 5 SNPs on chromosomes 5, 12, and 20 were significantly (P < or = 0.05) associated with LV mass after correction for multiple testing. One SNP (rs756529) is intragenic within KCNB1, which is dephosphorylated by calcineurin, a previously reported candidate gene for LV hypertrophy within this population.

CONCLUSION: These findings suggest KCNB1 may be involved in the development of LV hypertrophy in humans.

Author List

Arnett DK, Li N, Tang W, Rao DC, Devereux RB, Claas SA, Kraemer R, Broeckel U

Author

Ulrich Broeckel MD Chief, Center Associate Director, Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aged
Case-Control Studies
Echocardiography, Doppler
Female
Genetic Markers
Genome-Wide Association Study
Genotype
Humans
Hypertrophy, Left Ventricular
Male
Middle Aged
Polymorphism, Single Nucleotide
Risk Factors
Shab Potassium Channels