Validation study of genetic associations with coronary artery disease on chromosome 3q13-21 and potential effect modification by smoking

Benjamin D. Horne, Elizabeth R. Hauser, Liyong Wang, Joseph B. Muhlestein, Jeffrey L. Anderson, John F. Carlquist, Svati H. Shah, William E. Kraus

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

The CATHGEN study reported associations of chromosome 3q13-21 genes (KALRN, MYLK, CDGAP, and GATA2) with early-onset coronary artery disease (CAD). This study attempted to independently validate those associations. Eleven single nucleotide polymorphisms (SNPs) were examined (rs10934490, rs16834817, rs6810298, rs9289231, rs12637456, rs1444768, rs1444754, rs4234218, rs2335052, rs3803, rs2713604) in patients (N = 1618) from the Intermountain Heart Collaborative Study (IHCS). Given the higher smoking prevalence in CATHGEN than IHCS (41% vs. 11% in controls, 74% vs. 29% in cases), smoking stratification and genotype-smoking interactions were evaluated. Suggestive association was found for GATA2 (rs2713604, p = 0.057, OR = 1.2). Among smokers, associations were found in CDGAP (rs10934490, p = 0.019, OR = 1.6) and KALRN (rs12637456, p = 0.011, OR = 2.0) and suggestive association was found in MYLK (rs16834871, p = 0.051, OR = 1.8, adjusting for gender). No SNP association was found among non-smokers, but smoking/SNP interactions were detected for CDGAP (rs10934491, p = 0.017) and KALRN (rs12637456, p = 0.010). Similar differences in SNP effects by smoking status were observed on re-analysis of CATHGEN. CAD associations were suggestive for GATA2 and among smokers significant post hoc associations were found in KALRN, MYLK, and CDGAP. Genetic risk conferred by some of these genes may be modified by smoking. Future CAD association studies of these and other genes should evaluate effect modification by smoking.

Original languageEnglish (US)
Pages (from-to)551-558
Number of pages8
JournalAnnals of Human Genetics
Volume73
Issue number6
DOIs
StatePublished - Nov 1 2009

    Fingerprint

Keywords

  • Coronary disease
  • Genetic association
  • Replication study
  • Smoking

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this