Meta-analyses of KIF6 Trp719Arg in coronary heart disease and statin therapeutic effect

PLoS One. 2012;7(12):e50126. doi: 10.1371/journal.pone.0050126. Epub 2012 Dec 7.

Abstract

Aims: The goal of our study is to assess the contribution of KIF6 Trp719Arg to both the risk of CHD and the efficacy of statin therapy in CHD patients.

Methods and results: Meta-analysis of 8 prospective studies among 77,400 Caucasians provides evidence that 719Arg increases the risk of CHD (P<0.001, HR = 1.27, 95% CI = 1.15-1.41). However, another meta-analysis of 7 case-control studies among 65,200 individuals fails to find a significant relationship between Trp719Arg and the risk of CHD (P = 0.642, OR = 1.02, 95% CI = 0.95-1.08). This suggests that the contribution of Trp719Arg to CHD varies in different ethnic groups. Additional meta-analysis also shows that statin therapy only benefit the vascular patients carry 719Arg allele (P<0.001, relative ratio (RR) = 0.60, 95% CI = 0.54-0.67). To examine the role of this genetic variant in CHD risk in Han Chinese, we have conducted a case-control study with 289 CHD cases, 193 non-CHD controls, and 329 unrelated healthy volunteers as healthy controls. On post hoc analysis, significant allele frequency difference of 719Arg is observed between female CHD cases and female total controls under the dominant model (P = 0.04, χ(2) = 4.228, df = 1, odd ratio (OR) = 1.979, 95% confidence interval (CI) = 1.023-3.828). Similar trends are observed for post hoc analysis between female CHD cases and female healthy controls (dominant model: P = 0.04, χ(2) = 4.231, df = 1, OR = 2.015, 95% CI = 1.024-3.964). Non-genetic CHD risk factors are not controlled in these analyses.

Conclusions: Our meta-analysis demonstrates the role of Trp719Arg of KIF6 gene in the risk of CHD in Caucasians. The meta-analysis also suggests the role of this variant in statin therapeutic response in vascular diseases. Our case-control study suggests that Trp719Arg of KIF6 gene is associated with CHD in female Han Chinese through a post hoc analysis.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Case-Control Studies
  • Coronary Disease / drug therapy*
  • Coronary Disease / genetics*
  • Female
  • Gene Frequency
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Kinesins / genetics*
  • Male
  • Sex Factors
  • Treatment Outcome
  • White People / genetics

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • KIF6 protein, human
  • Kinesins

Grants and funding

The research was supported by grants from: National Natural Science Foundation of China (31100919 and 30772155), K.C. Wong Magna Fund in Ningbo University, Zhejiang Provincial Program for the Cultivation of High level Innovative Health Talents, Natural Science Foundation of Zhejiang Province (Y206608), Youth and Doctor Foundation of Ningbo (2005A610016), Zhejiang Provincial Natural Science Foundation (No. Y2100240), and Ningbo Natural Science Foundation (No. 2009A610142). The authors gratefully acknowledge the support of K.C. Wong Education Foundation, Hong Kong. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.