title: A potential regulatory single nucleotide polymorphism in the promoter of the Klotho gene may be associated with essential hypertension in the Chinese Han population.
abstract: 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.
authors.affiliation: Department of Geriatrics, Southwest Hospital, Third Military Medical University, Shapingba District, Chongqing 400038, PR China.
authors.forename: Hu-Lin
authors.initials: HL
authors.lastname: Wang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xu
authors.forename: Zhang
authors.initials: Z
authors.lastname: Wang
authors.forename: Yi-Hua
authors.initials: YH
authors.lastname: Zhang
authors.forename: Liang-Yi
authors.initials: LY
authors.lastname: Si
authors.forename: Xue-Jun
authors.initials: XJ
authors.lastname: Li
authors.forename: Qi-Hong
authors.initials: QH
authors.lastname: Yang
authors.forename: Hang
authors.initials: H
authors.lastname: Xiao
mesh_terms: 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*
chemical_list: D005966:Glucuronidase; D000090265:Klotho Proteins