Dataset Information

Investigation of KIF6 Trp719Arg in a case-control study of myocardial infarction: a Costa Rican population.

ABSTRACT: The 719Arg allele of KIF6 (rs20455) was associated with coronary events in Caucasian participants of five prospective studies. We investigated whether this KIF6 variant was associated with non-fatal myocardial infarction (MI) in a case-control study of an admixed population from the Central Valley of Costa Rica. Genotypes of the KIF6 variant were determined for 4,134 men and women. Cases (1,987) had survived a first MI; controls (2,147) had no history of MI and were matched to cases by age, sex, and area of residence. We tested the association between the KIF6 719Arg allele and non-fatal MI by conditional logistic regression and adjusted for admixture of founder populations.Compared with the reference Trp/Trp homozygotes, KIF6 719Arg carriers were not at significantly higher risk for non-fatal MI in this study after adjustment for traditional risk factors or admixture (OR= 1.12; 95%CI, 0.98-1.28). Heterozygotes of the KIF6 Trp719Arg variant were at increased risk of non-fatal MI: the adjusted odds ratio was 1.16 (95% confidence interval, 1.01-1.34), but this association would not be significant after a multiple testing correction.We found that carriers of the KIF6 719Arg allele were not at increased risk of non-fatal MI in a case-control study of Costa Ricans living in the Central Valley of Costa Rica.

SUBMITTER: Bare LA

PROVIDER: S-EPMC2947524 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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Investigation of KIF6 Trp719Arg in a case-control study of myocardial infarction: a Costa Rican population.

Bare Lance A LA Ruiz-Narvaéz Edward A EA Tong Carmen H CH Arellano Andre R AR Rowland Charles M CM Catanese Joseph J JJ Sacks Frank M FM Devlin James J JJ Campos Hannia H

PloS one 20100929 9

<h4>Background and methodology</h4>The 719Arg allele of KIF6 (rs20455) was associated with coronary events in Caucasian participants of five prospective studies. We investigated whether this KIF6 variant was associated with non-fatal myocardial infarction (MI) in a case-control study of an admixed population from the Central Valley of Costa Rica. Genotypes of the KIF6 variant were determined for 4,134 men and women. Cases (1,987) had survived a first MI; controls (2,147) had no history of MI and ...[more]

PMID: 20927332

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Project description:Case-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.Ten 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.These 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

Investigation of KIF6 Trp719Arg in a case-control study of myocardial infarction: a Costa Rican population.

Publications

Investigation of KIF6 Trp719Arg in a case-control study of myocardial infarction: a Costa Rican population.

Similar Datasets

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