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. Copyright 2009 Elsevier B.V. All rights reserved.
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 humanKlotho 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 humanKlotho gene is associated with EH and may be a potential regulatory site. Copyright 2009 Elsevier B.V. All rights reserved.
Authors: Gwendalyn D King; CiDi Chen; Mickey M Huang; Ella Zeldich; Patricia L Brazee; Eli R Schuman; Maxime Robin; Gregory D Cuny; Marcie A Glicksman; Carmela R Abraham Journal: Biochem J Date: 2012-01-01 Impact factor: 3.857
Authors: Eman A Elghoroury; Fatina I Fadel; Manal F Elshamaa; Dina Kandil; Doaa M Salah; Marwa M El-Sonbaty; Hebatallah Farouk; Mona Raafat; Soha Nasr Journal: Pediatr Nephrol Date: 2018-01-08 Impact factor: 3.714