A potential regulatory single nucleotide polymorphism in the promoter of the Klotho gene may be associated with essential hypertension in the Chinese Han population

• Published in: Clinica chimica acta Vol. 411; no. 5; pp. 386 - 390
• Main Authors: Wang, Hu-Lin, Xu, Qiang, Wang, Zhang, Zhang, Yi-Hua, Si, Liang-Yi, Li, Xue-Jun, Yang, Qi-Hong, Xiao, Hang
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2010
• Subjects: Asian Continental Ancestry Group - genetics; China; DNA Mutational Analysis; Ethnic Groups - genetics; Female; Genetic Predisposition to Disease - genetics; Genetic screening; Glucuronidase - genetics; Humans; Hypertension; Hypertension - genetics; Male; Middle Aged; Polymerase Chain Reaction; Polymorphism, Single Nucleotide - genetics; Promoter Regions, Genetic - genetics; Reporter gene; Single nucleotide polymorphism; China; Hypertension; Reporter gene; Single nucleotide polymorphism; Genetic screening
• ISSN: 0009-8981; 1873-3492
• DOI: 10.1016/j.cca.2009.12.004

Mice with defects in the Klotho gene exhibit multiple aging phenotypes including arteriosclerosis. We hypothesised that the G-395A polymorphism in the promoter region of the human Klotho gene may contribute to the prevalence of Essential Hypertension (EH). We investigate whether the G-395A polymorphism of Klotho is associated with EH in a population consisting of 215 patients with EH and 220 non-hypertensive subjects. We also tested whether a G/A substitution at the G-395A site affected the transcription level in vitro through the dual-luciferase reporter assay. Differences in the genotype distributions of the G-395A polymorphism between the EH and non-hypertension groups are statistically significant ( P = 0.032). There are differential effects of age, gender and smoking status on the association of the G-395A polymorphism with EH; the G-395A polymorphism is significantly associated with EH in subjects over 60 years old, in females and in nonsmokers. A multiple logistic regression analysis indicated that the odds ratio for EH in the –395A allele carriers as compared with the control group was 0.593 ( P= 0.024) after adjusting for current traditional risk factors. The dual-luciferase reporter assay revealed that the –395A carrier of a 498-bp DNA fragment (containing the G-395A site) upstream of the Klotho gene has higher relative luciferase activity than the –395G carrier. The G-395A polymorphism of the human Klotho gene is associated with EH and may be a potential regulatory site.