J Korean Diabetes Assoc.  2005 May;29(3):189-197.

The Relationship Between the C1818T Polymorphism in Exon 4 of the klotho Gene with Fasting Glucose and Insulin Levels in Korean Women

Affiliations
  • 1Department of Internal Medicine and Radiology, Hallym University, Chunchon, Korea.
  • 2Department of Internal Medicine, Sungkyunkwan University School of Medicine, Seoul, Korea.
  • 3Department of Internal Medicine, The Catholic University of Korea, College of Medicine, Seoul, Korea.

Abstract

BACKGROUND: A novel gene, termed klotho has been identified as a suppressor of several aging phenotypes, and a genetic defect of klotho in mice resulted in a syndrome resembling human aging, i.e., a short lifespan, infertility, arteriosclerosis, skin atrophy, osteoporosis, and pulmonary emphysema. Since klotho mice also showed an abnormal glucose metabolism, we investigated the relationship between the C1818T polymorphism in exon 4 of the klotho gene and fasting glucose and insulin resistance in Korean women to observe its contribution to glucose metabolism.
METHODS
The weight, height, blood pressure, fasting blood glucose, insulin, and lipid profiles were measured in 241 women(mean age, 51.2+/-7.0yr) by using the standard methods. Homeostasis model assessment(HOMA)-insulin resistance(IR), the quantitative insulin sensitivity check index(QUICKI) and HOMAbeta-cell were calculated. The genotyping of the C1818T polymorphism in exon 4 of the klotho gene was performed by allelic discrimination with using a 5' nuclease polymerase chain reaction assay.
RESULTS
The allele frequencies were 0.805 for the C allele and 0.195 for the T allele, and they were in Hardy-Weinberg equilibrium(P=0.290). The mean fasting blood glucose(P= 0.005) and HOMA IR(P=0.035) were significantly higher in the T allele carriers compared with the non-carriers. After adjustment was made for age, fasting blood glucose was persistently significant(P=0.015), but the HOMA-IR became marginally significant(P=0.063). In the premenopausal women, the T allele carriers showed a higher mean fasting blood glucose(P=0.038), insulin(P=0.024), HOMA-IR(P=0.010), total cholesterol(P=0.039), and triglyceride levels(P=0.031) than in the non-carriers. After adjustment was made for age, the fasting blood glucose, insulin, HOMA-IR and triglyceride were persistently significant(P= 0.043, P=0.026, P=0.011, P=0.040). Also, the QUICKI, total cholesterol and low-density ilpo-protein cholesterol became marginally significant(P=0.073, P=0.061, P=0.098). For the postmenopausal women, the T allele carriers showed a tendency for higher mean fasting blood glucose levels(P=0.065) and lower HOMA beta-cell levels(P=0.085) than in the noncarriers. These differences became non-significant after adjustment was made for age.
CONCLUSION
We observed that the C1818T polymorphism in exon 4 of the klotho gene was partly associated with glucose metabolism in Korean women. Also, these data suggest that the C1818T polymorphism is related with some cardiovascular risk factors in Korean women. The mechanism linking this gene with glucose metabolism warrants further study

Keyword

Klotho; Polymorphism; Fasting Glucose; Insulin Resistance; Cardiovascular Risk Factors; Women

MeSH Terms

Aging
Alleles
Animals
Arteriosclerosis
Atrophy
Blood Glucose
Blood Pressure
Cholesterol
Discrimination (Psychology)
Exons*
Fasting*
Female
Gene Frequency
Glucose*
Homeostasis
Humans
Infertility
Insulin Resistance
Insulin*
Metabolism
Mice
Osteoporosis
Phenotype
Polymerase Chain Reaction
Pulmonary Emphysema
Risk Factors
Skin
Triglycerides
Blood Glucose
Cholesterol
Glucose
Insulin
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