Association of KIF6 Variant with Lipid Level and Angiographic Coronary Artery Disease Events Risk in the Han Chinese Population

Abstract

KIF6 is a class of molecular motor from the kinesin superfamily. Recently, multiple large studies consisting mainly of Europeans have shown that KIF6 Trp719Arg SNP may be a new predictive factor for coronary artery disease (CAD) event risk. The allelic frequency distribution of rs20455 is different in various populations, yet studies among the Han population, one of the largest ethnic groups in the World, have not been conducted. This study is aimed to evaluate the association of KIF6 Trp719Arg variant with angiographic CAD and serum lipid levels in the Han population from northern China. In this case-controlled study, peripheral blood samples were collected from 356 patients and 568 controls of Han Chinese origin. Genotyping was performed by a high-resolution melting curve. The impact of rs20455 on CAD and non-fatal MI was evaluated in a dominant genetic model with stepwise multiple regression analysis. There were no significant differences of genotypes and allele frequency between angiographic CAD and control groups (p > 0.05); however, that of MI and non-MI subgroups were significant differences (p < 0.05). After adjusting for significant risk factors, angiographic CAD risk was not significantly increased in 719Arg allele carriers compared with non-carriers. Further analysis revealed that the non-fatal MI risk and triglyceride levels were significantly higher in 719Arg allele carriers than non-carriers. In conclusion, KIF6 719Arg allele was not an independent risk factor for angiographic CAD susceptibility in Han populations from northern China. However, it was associated with a significantly higher TG level, which may indicate an increased myocardial infarction risk in angiographic CAD patients.

NovelKIF6Polymorphism Increases Susceptibility to Type 2 Diabetes Mellitus and Coronary Heart Disease in Han Chinese Men

“…Collectively, genome-wide association studies have identified SNPs in at least 95 loci, the combined effects of which account for approximately 10–12% of the total variance in HDL and TG levels [ 35 ]. Previously, we verified that the common KIF6 polymorphism Trp719Arg is involved in lipid metabolism and CHD, reporting that it was associated with significantly higher TG levels with increased myocardial infarction risk in angiographic CHD patients [ 24 ]. The characteristic features of diabetic dyslipidemia are increased concentrations of plasma TG and small dense LDL-C particles and decreased HDL-C [ 36 ].…”

“…The KIF6 gene spans a genomic region of about 390,000 base pairs on human chromosome 6p21, containing 23 exons and 22 introns [ 13 ]. Since 2007, there have been multiple large prospective and case-control studies on the association of a common KIF6 gene polymorphism—Trp719Arg single-nucleotide polymorphism (SNP) (rs20455)—with CHD risk [ 14 – 23 ], and a significant relationship between the KIF6 Trp719Arg polymorphism and CHD has been observed in several ethnic groups [ 15 , 18 , 21 , 22 , 24 – 26 ]. Accumulating evidence has suggested that KIF6 rs20455 may be a new predictive factor for risk of CHD occurrence and a genetic determinant of the plasma lipid level [ 24 , 25 , 27 – 29 ].…”

The Trp719Arg polymorphism of the KIF6 gene and coronary heart disease risk: systematic review and meta-analysis

“…There are several explanations for the present outcomes concerning the lack of association of Trp719Arg with CHD. First, there are differences in diagnosis in the population of patients and, second, the discrepancy of association between populations may be attributed to different genetic backgrounds and environmental factors [13, 16]. …”

Genotyping and meta-analysis of KIF6 Trp719Arg polymorphism in South Indian Coronary Artery Disease patients: A case–control study

“…Meta-analysis of the KIF6 Trp719Arg genotype from non-European populations ( Bare et al, 2010 , Bhanushali et al, 2011 , Peng et al, 2012 , Wu et al, 2012 ) was performed along with the data of the present study in both dominant and allelic models using fixed and random effects ( Helfenstein, 2002 ). The meta-analysis was carried out by comprehensive meta-analysis software [Biostat, USA].…”