American Heart Journal
Volume 154, Issue 3 , Pages 561-566, September 2007

Connexin37 (GJA4) genotype predicts survival after an acute coronary syndrome

  • David E. Lanfear, MD, MS

      Affiliations

    • Henry Ford Heart and Vascular Institute and Wayne State University, Detroit, MI
  • ,
  • Philip G. Jones, MS

      Affiliations

    • Mid America Heart Institute, Kansas City, MO
  • ,
  • Sharon Marsh, PhD

      Affiliations

    • Department of Medicine, Washington University School of Medicine, St Louis, MO
  • ,
  • Sharon Cresci, MD

      Affiliations

    • Cardiovascular Diseases Division, Department of Medicine, Washington University School of Medicine, St Louis, MO
  • ,
  • John A. Spertus, MD, MPH

      Affiliations

    • Mid America Heart Institute, Kansas City, MO
    • University of Missouri-Kansas City, Kansas City, MO
    • Corresponding Author InformationReprint requests: John Spertus, MD, MPH, Mid America Heart Institute, 4401 Wornall Road, Kansas City, MO 64111.
  • ,
  • Howard L. McLeod, PharmD

      Affiliations

    • Institute for Pharmacogenomics and Individualized Therapy, University of North Carolina, Chapel Hill, NC

Received 1 December 2006; accepted 29 April 2007. published online 08 June 2007.

Background

GJA4 1019 C > T, MMP3 −1171delA, and SERPINE1 −668delG genotypes have been associated with the risk of incident myocardial infarction. We tested the hypothesis that these genotypes would predict long-term mortality after an acute coronary syndrome (ACS).

Methods

We assembled a prospective cohort study on 726 patients with ACS admitted between March 2000 and October 2001. Kaplan-Meier estimates and Cox proportional hazards models of 3-year mortality adjusted for age, race, ACS type, prior heart failure, diabetes, and revascularization were used to compare groups.

Results

The GJA4 1019 C > T genotype was significantly related to mortality over 3 years (8.3% vs 14%, for the C/C vs T allele carriers; P = .02), with an adjusted hazard ratio of 1.7 (95% confidence interval 1.05-2.8, P = .03). This finding was consistent in both men and women (hazard ratio = 1.9 and 1.7, respectively) with no significant sex interaction (P = .8). The MMP3 −1171delA and SERPINE1 −668delG genotypes were not significantly related to mortality in the overall population (all P > .4).

Conclusions

GJA4 1019 C > T genotype predicted risk of death after an ACS, whereas the MMP3 and SERPINE1 genotypes did not. The GJA4 1019 C > T polymorphism may warrant integration into comprehensive risk stratification algorithms for patients with ACS.

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 This work was supported in part by R01 HS11282-01 from the Agency for Healthcare Research and Quality, the NIH Pharmacogenetics research network (U01 GM63340), a Heart Failure Society of America Research Fellowship grant, and NIH SCCOR (P50 HL077113).

 Dr Howard L. McLeod is a member of an advisory board for the US Food and Drug Administration.

PII: S0002-8703(07)00384-5

doi:10.1016/j.ahj.2007.04.059

American Heart Journal
Volume 154, Issue 3 , Pages 561-566, September 2007