Investigation of KIF6 Trp719Arg in a Case-Control Study of Myocardial Infarction: A Costa Rican Population

Background and Methodology 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. Principal Findings 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. Conclusions/Significance 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. Introduction Kinesins are a superfamily of homodimeric motor proteins that transport cellular cargos (e.g., proteins, vesicles, or organelles) along microtubules in an ATP dependent process. A single nucleotide polymorphism (SNP) in the gene for the KIF6 protein—a member of the kinesin 9 family—has been reported to be associated with coronary heart disease (CHD) and event reduction during statin therapy[2]. In Caucasians, carriers of the 719Arg allele of this SNP (rs20455) were at increased risk for coronary events in 5 prospective studies: the Atherosclerosis Risk in Communities (ARIC) study, the Cardiovascular Health Study (CHS) , the Women's Health Study (WHS), and in the placebo groups of both the Cholesterol and Recurrent Events (CARE) study and the West of Scotland Coronary Prevention Study (WOSCOPS), In contrast to these prospective studies, KIF6 Trp719Arg was not associated with coronary artery disease (CAD) in two recently reported case-control studies: the Ottawa Heart Genomics study and the Welcome Trust Case-Control Consortium study Only limited data are available regarding whether the KIF6 719Arg allele is associated with CHD in other ethnic populations. For example, among African Americans in ARIC, each allele of KIF6 719Arg increased the risk for incident CHD by 1.23-fold (95%CI, 0.99–1.52), and among African Americans in CHS, carriers of the KIF6 719Arg allele had a hazard ratio for incident myocardial infarction (MI) of 4.14 (90%CI, 0.79–21.77), compared with noncarriers[4]. Thus, although the associations between the KIF6 719Arg allele and CHD were not statistically significant in the small African American study populations in ARIC and CHS, these results suggested that the KIF6 719Arg allele may be associated with CHD in ethnic populations other than Caucasians. Therefore, we asked whether the KIF6 719Arg allele is associated with MI in a Hispanic population from Costa Rica. Results The characteristics of cases with myocardial infarction and population-based controls from the Central Valley of Costa Rica used in this study are shown in Table 1. Age, sex, and residence (i.e., matched characteristics) did not differ significantly between cases and controls (Table 1). Other CHD risk factors (smoking, history of hypertension, family history of MI, and waist-to-hip ratio) were higher in cases than in controls (Table 1). The genotypes of the KIF6 SNP (rs20455) that cause a Trp719Arg variation did not deviate from the distribution expected under Hardy–Weinberg equilibrium (P = 0.38); the frequency of the minor allele (KIF6 719Arg) was 0.36 in the control subjects. Characteristics of Cases and Controls. We found that carriers of one or two copies of the KIF6 719Arg variant were not at increased risk of MI (OR = 1.12; 95%CI, 0.98–1.28; Table 2). Although the risk estimate for heterozygotes of the KIF6 variant (Trp/Arg), compared with major allele homozygotes (Trp/Trp), was 1.15 (95%CI 1.00–1.33; Table 2) after adjusting for potentially confounding risk factors and admixture in this Costa Rican population, this association would not be significant if corrected for the testing of multiple KIF6 719Arg carrier groups. Homozygotes of the KIF6 variant (Arg/Arg) were not at increased risk of MI, compared with major allele homozygotes (Trp/Trp)

Investigation of KIF6 Trp719Arg in a Case-Control Study of Myocardial Infarction: A Costa Rican Population

Background and Methodology: 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. Principal Findings: 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. Conclusions/Significance: We found that carriers of the KIF6 719Arg allele were not at increased risk of non-fatal MI in