The Change Of The Aldose Reductase Activity And The C-106T Polymorphism Of Aldose Reductase Gene In Essential Hypertension

Background:Aldose Reductase(AR/ALR2) is one member of NADPH-dependent aldo-keto reductase superfamily and is sensitive to ROS,which is monosonic and widely distributed in the human body.AR is implicated in diabetic chronic complications.Moreover,the expression of AR also increases under several pathological conditions associated with increased oxidative stress such as myocardial ischemia,vascular inflammation,and restenosis.Extensive investigations show that AR is involved in cell proliferation,TNF-α-mediated inflammatory response and redox-sensitive signaling pathways,which are related to vascular smooth muscle cell(VSMC) proliferation.AR inhibitors prevent VSMC growth.ROS can activate AR,and activated AR may accelerate inflammatory response and cell growth.Essential hypertension(EH) is an inflammatory response and oxidative stress,and the pathological process of EH involves changes in VSMC growth,apoptosis/anoikis,cell migration,inflammation,and fibrosis.Moreover,we have previously shown that AR activities of SHR erythrocytes and cardiac muscle were significantly increased compared to control group.Together,we speculate that there is an alteration of erythrocytes AR activity in EH patients,and AR may be implicated in cardiovascular remodeling.A single nucleotide polymorphism in the promoter region(C-106T) of AR gene may be associated with EH.Objective:To examine whether there is a change of erythrocytes AR activity in Essential Hypertension.To find out the frequences of AR C-106T polymorphism in EH patients and the control group.Method:The AR activity of erythrocytes was measured by NADP-generating fluorimetry.A single nucleotide polymorphism in the promoter region(C-106T) was genotyped by PCR-RFLP method. Statistical analyses were performed using SPSS for Windows version 13.0.Data was evaluated by t-test,chi-square.P <0.05 is thought to be statistically significant.Results:1) Erythrocytes AR activity in EH was 0.0419±0.003 U/g·Hb(n=5),and was higher than those in the control group which was 0.0400±0.006 U/g·Hb(n=6).But there was no statistical significance(P =0.528).2) The frequency of AR -106T allele in Chinese(n=285) was 13.9% (95%CI:11.0%-17.0%),which was lower than that in Japanese(n=712, 18.4%,P = 0.015 ),Brazilians(n=62,34.7%,P <0.001) and Australians (n=240,36.9%,P <0.001),which indicated that this polymorphism have ethnic differences.The frequencies of AR -106T allele in EH patients(n=148) and controls(n=137) are 15.9(95%CI:11.9%-20.5%), 11.7%(95%CI:8.1%-16.1%),respectively,but this difference is not statistically significant(P=0.147).Conclusion:1.The change of erythrocytes AR activity in EH had no statistical significance.2.AR C-106T mutation presented ethnic differences.3.There was no significant differences found about the frequencies of AR -106T allele between EH patients and controls.