Relationship between polymorphisms G395A in promoter and C1818T in exon 4 of the KLOTHO gene with glucose metabolism and cardiovascular risk factors in Korean women.

ABSTRACT

BACKGROUND: Recently, klotho has been proposed as a link between cardiovascular diseases and premature aging, but the relationship between KLOTHO genes and cardiovascular risk factors, especially glucose metabolism, in humans is unclear. OBJECTIVES: We investigate the relationship between polymorphisms G395A in promoter and C1818T in exon 4 of the KLOTHO gene with glucose metabolism and cardiovascular risk factors in Korean women. MATERIAL AND METHODS: In 251 women (mean age 51.3+/-6.9 yr), body mass index (BMI), waist circumference, blood pressure, fasting plasma glucose, insulin and lipid profiles were measured. The genotyping of polymorphisms G395A in promoter and C1818T in exon 4 of the KLOTHO gene was performed by allelic discrimination using a 5' nuclease polymerase chain reaction assay. RESULTS: Allele frequencies of G395A polymorphism was 0.829 for the G allele and 0.171 for the A allele and allele frequencies of C1818T polymorphism were 0.804 for the C allele and 0.196 for the T allele, both of which were in compliance with Hardy-Weinberg equilibrium and the two polymorphisms were in linkage disequilibrium (D'=0.43, p<0.01). Mean systolic blood pressure was significantly higher in A allele carriers of G395A polymorphism compared with non-carriers, and the significance was persistent even after adjustment for age and BMI. Mean fasting plasma glucose was significantly higher in T allele carriers of C1818T polymorphism compared with non-carriers, and the significance was persistent even after adjustment for age and BMI. Subjects without any minor allele from either single nucleotide polymorphisms (SNP) had significantly lower mean values for systolic, diastolic blood pressure and fasting plasma glucose levels compared with subjects with both minor allele from either SNP. CONCLUSIONS: We observed that KLOTHO G395A polymorphism was associated with blood pressure and KLOTHO C1818T polymorphism was associated with glucose metabolism in Korean women. Further studies are needed to clarify this relationship.