sábado, 30 de octubre de 2010
No association between KIF6 Trp719Arg polymorphism and CAD risk
Assimes T. J Am Coll Cardiol. 2010; doi:10.1016/j.jacc.2010.06.022.
Topol E. J Am Coll Cardiol. 2010; doi:10.1016/j.jacc.2010.06.023.
Patients with nonfatal coronary artery disease who had KIF6 Trp719Arg polymorphism genotyped did not have an increased risk for developing clinical coronary artery disease, according to recent findings published in the Journal of American College of Cardiology.
Researchers included participants with nonfatal CAD (cases, n=17,000; controls, n=39,369) of European descent, as well as a modest number from other regions, from 19 international case-control studies. The KIF6 Trp719Arg polymorphism (rs20455), which was found in earlier studies to be associated with CAD development, was genotyped either as part of a genome-wide association study or in a formal attempt to replicate the initial positive reports
According to study results, carriers of the 719Arg allele vs. noncarriers did not have an increased risk for CAD in any of the 19 studies. The researchers ruled out with high degree of confidence an increase of at least 2% in the risk for CAD among European 719Arg carriers with regression analyses and fixed-effects meta-analyses. Additionally, among a subset of European 719Arg carriers with early onset disease (men, <50 years old; women, <60 years old), there was no reported increased risk for CAD vs. either similarly aged controls or non-European subgroups.
“Our findings question not only the usefulness of the KIF6 test in identifying subjects at increased risk of incident or recurrent CAD but also its usefulness in identifying subjects most likely to benefit from statins,” the researchers wrote. “Although we could not test the latter hypothesis directly, the previously reported interaction between genotype and benefit from statins is largely dependent on the validity of the association among subjects not taking statins, which could not be replicated in this study.”
Eric J. Topol, MD, and Samir B. Damani, MD, PharmD, both of the Scripps Translational Science Institute and the Scripps Research Institute, La Jolla, Calif., in accompanying editorial, said there is meta-analysis for strongly refuting the KIF6 link to CAD.
“Such genetic and pharmacogenetic markers must be accompanied by stringent vetting by investigators in well-designed, hypothesis-free, genome-wide studies before promoting their use in clinical practice,” they concluded. “Going forward, the KIF6 story should serve as a valuable reminder of the potential pitfalls present in prematurely adopting a genomic test without sufficient evidence.”
See Related Articles
Adults, younger patients with congenital heart disease had similar catheter ablation IART outcomes
CYP2C19 allele linked with increased risk for major adverse CV events in patients given clopidogrel for PCI
Hepatitis C increased risks for cerebrovascular-related death
No association between <I>KIF6</I> Trp719Arg polymorphism and CAD risk