Replication of genetic association studies in aortic stenosis in adults

Authors: Gaudreault, NathalieDucharme, ValérieLamontagne, MaximeGuauque-Olarte, SandraMathieu, PatrickPibarot, PhilippeBossé, Yohan
Abstract: Only a handful of studies have attempted to unravel the genetic architecture of calcific aortic valve stenosis (AS). The goal of this study was to validate genes previously associated with AS. Seven genes were assessed: APOB, APOE, CTGF, IL10, PTH, TGFB1, and VDR. Each gene was tested for a comprehensive set of single-nucleotide polymorphisms (SNPs). SNPs were genotyped in 457 patients who underwent surgical aortic valve replacement, and allele frequencies were compared to 3,294 controls. A missense mutation in the APOB gene was significantly associated with AS (rs1042031, E4181K, p = 0.00001). A second SNP located 5.6 kilobases downstream of the APOB stop codon was also associated with the disease (rs6725189, p = 0.000013). Six SNPs surrounding the IL10 locus were strongly associated with AS (0.02 > p > 6.2 × 10¯¹¹). The most compelling association for IL10 was found with a promoter polymorphism (rs1800872) well known to regulate the production of the encoded anti-inflammatory cytokine. The frequency of the low-producing allele was greater in cases compared to controls (30% vs 20%, p = 6.2 × 10¯¹¹). SNPs in PTH, TGFB1, and VDR had nominal p values <0.05 but did not resist Bonferroni correction. In conclusion, this study suggests that subjects carrying specific polymorphisms in the IL10 and APOB genes are at higher risk for developing AS.
Document Type: Article de recherche
Issue Date: 1 November 2011
Open Access Date: Restricted access
Document version: VoR
Permalink: http://hdl.handle.net/20.500.11794/7819
This document was published in: The American journal of cardiology, Vol. 108 (9), 1305–1310 (2011)
http://www.sciencedirect.com/science/article/pii/S0002914911022429
Elsevier
Alternative version: 10.1016/j.amjcard.2011.06.050
http://www.ncbi.nlm.nih.gov/pubmed/21855833
Collection:Articles publiés dans des revues avec comité de lecture

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