Dataset Information

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

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, ?(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, ?(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.

SUBMITTER: Peng P

PROVIDER: S-EPMC3517591 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

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

Peng Ping P Lian Jiangfang J Huang R Stephanie RS Xu Limin L Huang Yi Y Ba Yanna Y Yang Xi X Huang Xiaoyan X Dong Changzhen C Zhang Lina L Ye Meng M Zhou Jianqing J Duan Shiwei S

PloS one 20121207 12

<h4>Aims</h4>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.<h4>Methods and results</h4>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 ...[more]

PMID: 23236363

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Project description:BackgroundCase-control studies typically exclude fatal endpoints from the case set, which we hypothesize will substantially underestimate risk if survival is genotype-dependent. The loss of fatal cases is particularly nontrivial for studies of coronary heart disease (CHD) because of significantly reduced survival (34% one-year fatality following a coronary attack). A case in point is the KIF6 Trp719Arg polymorphism (rs20455). Whereas six prospective studies have shown that carriers of the KIF6 Trp719Arg risk allele have 20% to 50% greater CHD risk than non-carriers, several cross-sectional case-control studies failed to show that carrier status is related to CHD. Computer simulations were therefore employed to assess the impact of the loss of fatal events on gene associations in cross-sectional case-control studies, using KIF6 Trp719Arg as an example.ResultsTen replicates of 1,000,000 observations each were generated reflecting Canadian demographics. Cardiovascular disease (CVD) risks were assigned by the Framingham equation and events distributed among KIF6 Trp719Arg genotypes according to published prospective studies. Logistic regression analysis was used to estimate odds ratios between KIF6 genotypes. Results were examined for 33%, 41.5%, and 50% fatality rates for incident CVD.In the absence of any difference in percent fatalities between genotypes, the odds ratios (carriers vs. noncarriers) were unaffected by survival bias, otherwise the odds ratios were increasingly attenuated as the disparity between fatality rates increased between genotypes. Additional simulations demonstrated that statin usage, shown in four clinical trials to substantially reduce the excess CHD risk in the KIF6 719Arg variant, should also attenuate the KIF6 719Arg odds ratio in case-control studies.ConclusionsThese computer simulations show that exclusions of prior CHD fatalities attenuate odds ratios of case-control studies in proportion to the difference in the percent fatalities between genotypes. Disproportionate CHD survival for KIF6 Trip719Arg carriers is suggested by their 50% greater risk for recurrent myocardial infarction. This, and the attenuation of KIF6 719Arg carrier risk with statin use, may explain the genotype's weak association with CHD in cross-sectional case-control studies. The results may be relevant to the underestimation of risk in cross-sectional case-control studies of other genetic CHD-risk factors affecting survival.

Dataset Information

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

Aims

Methods and results

Conclusions

Publications

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

Similar Datasets

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