The association of KLOTHO gene polymorphism with coronary artery disease in Korean subjects

Rhee, Eun Jung; Kim, Se Yeon; Jung, Chan Hee; Kim, Byung Jin; Sung, Ki Chul; Kim, Bum Su; Lee, Won Young; Kang, Jin Ho; Oh, Ki Won; Lee, Man Ho; Kim, Sun Woo; Park, Jung Roe

Abstract

BACKGROUND: Klotho knock-out mouse is being thought as a good animal model for human aging and these mice show typically severe atherosclerosis of large arteries. Recent studies report on the association of KLOTHO gene mutation with cardiovascular diseases in humans. We observed the frequencies of G395A in promoter and C1818T in exon 4 of KLOTHO gene and investigated their relationships with the presence of coronary artery disease (CAD) in those patients underwent coronary angiograms
METHODS
Total 168 subjects (mean age 58 years, 26-87 years) who underwent coronary angiograms due to chest pain were enrolled and blood pressure, body mass index, fasting blood glucose and lipid profiles were measured in all subjects. Genotypings were performed with real-time polymerase chain reaction from sampled blood.
RESULTS
The allele frequencies of G395A were 0.872 for G allele and 0.128 for A allele and those of C1818T were 0.830 for C allele and 0.170 for T allele. Both were in compliance with Hardy-Weinberg equilibrium (p=0.99, p=0.82). When the subjects were classified into four groups according to the number of stenotic vessels, there were no differences among the mean values of the cardiovascular risk factors, except high-density lipoprotein cholesterol, that showed a significant difference between that of normal and the diseased vessel groups. There were no differences in the prevalence of CAD according to the genotypes of G395A polymorphism, but for C1818T polymorphism, subjects with T allele showed lower prevalence of CAD than those with CC genotype. When the subjects were divided into two groups according to age, in the group under 60 years of age, T allele carriers of C1818T polymorphism showed lower prevalence of CAD than non-carriers. In the group older than 60 years, A allele carriers of G395A polymorphism showed lower prevalence of CAD than non-carriers.
CONCLUSIONS
The frequencies of KLOTHO G395A and C1818T polymorphisms in Koreans were observed similarly to those reported in other Asian races and the phenotypic expression on CAD was different according to age groups. These results infer the possibility of KLOTHO gene as the candidate gene of atherosclerosis in humans, which needs further research.