The differential effects of age on the association of KLOTHO gene polymorphisms with coronary artery disease

The Klotho knockout mouse is thought to be a good animal model for human aging. Recent studies have reported on the association of KLOTHO gene mutation with cardiovascular disease in humans. We observed the frequencies of single nucleotide polymorphisms, that is, G-395A in the promoter region, C1818T in exon 4, and a functional variant, KL-VS, of KLOTHO gene in Koreans, and we investigated their relationships with the presence of coronary artery disease (CAD) in patients who had undergone coronary angiograms. A total of 274 subjects who underwent coronary angiograms because of chest pain were enrolled, and their blood pressure, body mass index, fasting blood glucose level, and lipid profiles were measured. Genotypings were performed on samples of their blood with real-time polymerase chain reaction. Two single nucleotide polymorphisms, G-395A and C1818T, complied with Hardy-Weinberg equilibrium. For the KL-VS genotype, I homozygote subject for the adverse allele was detected among the entire population (GG for F352V and CC for C370S). When the subjects were classified into 4 groups according to the number of stenotic vessels, there were no differences among the mean values of the cardiovascular risk factors, except for age and the fasting blood glucose levels, which showed a significant difference between that of the normal and the diseased vessel groups. There were no differences in the prevalence of CAD according to the genotypes of the G-395A polymorphism; however, for the C1818T polymorphism, those subjects with the T allele showed a lower prevalence of CAD than those with the CC genotype. When the subjects were divided into 2 groups according to age, in the group younger than 60 years, T allele carriers of the C1818T polymorphism showed a lower prevalence of CAD than did the noncarriers. In the group older than 60 years, A allele carriers of the G-395A polymorphism showed a lower prevalence of CAD than did the noncarriers. On the haplotype analysis, the GG-CC haplotype showed an increased risk for CAD with an odds ratio of 2.594 (95% confidence interval, 1.385-4.858; P = 0.003). Differential effects of age were observed in the association of KLOTHO G-395A and C1818T polymorphisms with CAD in Koreans. The KL-VS variant seems to be rarely found in the Korean population. These results infer the possibility of the KLOTHO gene being a candidate gene of atherosclerosis in humans, and further research on this topic needs to be done. (c) 2006 Elsevier Inc. All rights reserved.