Genetic variation in NCAM1 contributes to left ventricular wall thickness in hypertensive families

Academic Article

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. 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. Copyright © 2011 American Heart Association. All rights reserved.
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    Digital Object Identifier (doi)

    Author List

  • Arnett DK; Meyers KJ; Devereux RB; Tiwari HK; Gu CC; Vaughan LK; Perry RT; Patki A; Claas SA; Sun YV
  • Start Page

  • 279
  • End Page

  • 283
  • Volume

  • 108
  • Issue

  • 3