Faculty Collaboration Database

Genetic variation in NCAM1 contributes to left ventricular wall thickness in hypertensive families. Circ Res 2011 Feb 04;108(3):279-83

Date

01/08/2011

Pubmed ID

21212386

Pubmed Central ID

PMC3328104

DOI

10.1161/CIRCRESAHA.110.239210

Scopus ID

2-s2.0-79751535563 (requires institutional sign-in at Scopus site)   42 Citations

Abstract

RATIONALE: Left ventricular (LV) mass and related phenotypes are heritable, important predictors of cardiovascular disease, particularly in hypertensive individuals.

OBJECTIVE: Identify genetic predictors of echocardiographic phenotypes in hypertensive families.

METHODS AND RESULTS: A multistage genome-wide association study (GWAS) was conducted in hypertensive-ascertained black families (HyperGEN, stage I; GENOA, stage II); findings were replicated in HyperGEN white families (stage III). Echocardiograms were collected using a common protocol, and participants were genotyped with the Affymetrix Genome-Wide Human SNP 6.0 Array. The following were analyzed using mixed models adjusted for ancestry: in stages I and II, 1258 and 989 blacks, respectively; and in stage III, 1316 whites. Phenotypes included LV mass, LV internal dimension (LVID), wall thicknesses (posterior [PWT] and intraventricular septum [IVST]), and relative wall thickness (RWT). In stage I, 5 single nucleotide polymorphisms (SNPs) had P≤10(-6). In stage II, 1 SNP (rs1436109; NCAM1 intron 1) replicated with the same phenotype (PWT, P=0.025) in addition to RWT (P=0.032). In stage III, rs1436109 was associated with RWT (P=5.47×10(-4)) and LVID (P=1.86×10(-4)). Fisher combined probability value for all stages was RWT=3.80×10(-9), PWT=3.12×10(-7), IVST=8.69×10(-7), LV mass=2.52×10(-3), and LVID=4.80×10(-4).

CONCLUSIONS: This GWAS conducted in hypertensive families identified a variant in NCAM1 associated with LV wall thickness and RWT. NCAM is upregulated during the remodeling period of hypertrophy to heart failure in Dahl salt-sensitive rats. Our initial screening in hypertensive blacks may have provided the context for this novel locus.

Author List

Arnett DK, Meyers KJ, Devereux RB, Tiwari HK, Gu CC, Vaughan LK, Perry RT, Patki A, Claas SA, Sun YV, Broeckel U, Kardia SL

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

Adult
Aged
CD56 Antigen
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
Heart Ventricles
Humans
Hypertension
Hypertrophy, Left Ventricular
Male
Middle Aged
Phenotype
Polymorphism, Single Nucleotide
Ultrasonography