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


METHODS
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.


RESULTS
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 60years 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.


CONCLUSIONS
The G-395A polymorphism of the human Klotho gene is associated with EH and may be a potential regulatory site.
Wang
Hu-Lin
HL
Department of Geriatrics, Southwest Hospital, Third Military Medical University, Shapingba District, Chongqing 400038, PR China.
Xu
Qiang
Q
Wang
Zhang
Z
Zhang
Yi-Hua
YH
Si
Liang-Yi
LY
Li
Xue-Jun
XJ
Yang
Qi-Hong
QH
Xiao
Hang
H
D044466:Asian People / Q000235:genetics*; D002681:China; D004252:DNA Mutational Analysis; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005966:Glucuronidase / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D000090265:Klotho Proteins; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*
D005966:Glucuronidase; D000090265:Klotho Proteins