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

Abstract

The KIF6 719Arg allele is an interesting genomic variant widely screened in various populations and is reported to be associated with the risk of Coronary Artery Disease (CAD) and statin treatment outcome. Recent population based clinical studies and large-scale meta-analyses pondered over the role of 719Arg variant in CAD risk and treatment response. We screened the KIF6 Trp719Arg polymorphism (rs20455) in south Indian CAD patients in a case–control approach. A total of 1042 samples (510 CAD patients and 532 controls) were screened for the KIF6 Trp719Arg SNP by TaqMan SNP genotyping assay, followed by meta-analysis of the genotype data of non-Europeans reports. The 719Arg risk genotype (GG) was observed in 29.6% of CAD cases and in 30.1% of controls with an odds ratio (OR) of 1.07 (95% CI: 0.76–1.50), p value = 0.709. No significant difference in the genotype frequency was observed between CAD and controls in both dominant model (AG + GG vs AA) and allelic model (719Arg vs 719Trp) with an OR of 1.11 (p = 0.491) and 1.03 (p = 0.767), respectively. The covariate analysis indicated that smoking & alcohol consumption increased the risk for MI among CAD patients. Meta-analysis showed that the KIF6 719Arg allele is not associated with CAD risk in both fixed effect (p = 0.515, OR = 1.023, 95% CI = 0.956–1.094) and random effect (p = 0.547, OR = 1.022, 95% CI = 0.953–1.096). The symmetrical shape of the Egger's funnel plots revealed that there is no publication bias. These results suggest that there is no association of KIF6 719Arg allele with CAD risk in South Indian population and the meta-analysis confirms the same among non-European population.

Relationship between Lipid Phenotypes, Overweight, Lipid Lowering Drug Response and KIF6 and HMG-CoA Genotypes in a Subset of the Brisighella Heart Study Population

“…Besides the HMG-CoA polymorphism, we also observed a correlation between KIF6 rs20455 and HDL level; in particular, homozygous carriers of the G-minor allele showed higher serum HDL-C. The rs20455 variant is a non-synonymous polymorphism, leading to the replacement of a non-polar Trp with a basic Arg at codon 719, widely screened in relation to cardiovascular events, serum lipids and statin treatment outcome in various populations, with contrasting results [ 20 , 21 , 42 , 43 , 44 , 45 , 46 , 47 ]. To the best of our knowledge, our study is the first reporting an association with the KIF6 719Arg variant and HDL-C, while no apparent difference or opposite results were observed in previous studies [ 20 , 21 , 42 , 43 , 44 , 45 , 46 , 47 ].…”

Impact of KIF6 Trp719Arg gene variant on Coronary Artery Disease Development

“…During acute myocardial Infarction (MI), the mobilization of the endothelial progenitor cells (EPC) from bone marrow induces neovascularization through endothelial colony-forming cells (ECFC) causing infarct size reduction. KIF6 Trp719Arg patients had no ECFC cells and this may be due to the replacement of 'Trp' residue with 'Arg' amino acid causing alteration of KIF6's cargo activity resulting in a lack of ECFC mobilization from the bone marrow (40). KIF6 (rs20455; A > G) patients had greater myocardial damage due to the lower ECFC level.…”

Association between rs20456 and rs6930913 of Kinesin-Like Family 6 and Hypertension in a Chinese Cohort

“…KIF6 protein has been detected in a variety of tissues, including coronary arteries and other vascular tissues [16]. KIF6 polymorphisms have been reported to be associated with epicardial coronary endothelial dysfunction, interrupting intracellular transport in endothelial cells to develop CHD and different statin treatment outcomes [5,[17][18][19][20][21][22]. According to a recent study, KIF6 has a specific role for endothelial cells ciliogenesis in vertebrates [23].…”