The Association Of Klotho G-395A Gene Polymorphism And Left Ventricular Hypertrophy In Maintenance Hemodialysis Patients

Objective: To explore the relationship between Klotho G-395 A polymorphism and left ventricular hypertrophy for maintenance hemodialysis.Methods: 146 patiens who received maintenance hemodialysis(MHD)in Blood Purification Centres of our hospital and 70 health controls were enrolled in the study.Blood samples were collected from all of the participators to be used for DNA extraction and polymerase chain reaction(PCR)amplification.The single nucleotide polymorphism(Single Nucleotide Polymorphism,SNP)at G-395 A site of klotho gene was detected by a generation sequencing method.The levels of klotho protein and fibroblast growth factor(FGF23)were examined by enzyme linked immunosorbent assay(ELISA).The general and clinical biochemical data of all patients were collected.We compared the level of klotho protein,FGF23 and other clinical biochemical indexes between MHD group and control group,and the difference of klotho protein,FGF23 and clinical biochemical indexes among different genotypes were also analyzed in MHD group.Left ventricular end-systolic diameter(LVSd),left ventricular enddiastolic diameter(LVDd),left ventricular posterior wall thickness(LVPWT)and interventricular septal thickness(IVST)were evaluated by echocardiography in MHD patients.The left ventricular mass index(LVMI)was calculated according to the formula to evaluate the presence of left ventricular hypertrophy(LVH)in MHD patients.They were divided into two groups: LVH group and no LVH group.Compare the genotype distribution and the difference of biochemical indexes between the two groups,we aimed to explore the relationship between genotype distribution and LVH in MHD patients.Results:(1)The genotype frequencies of the SNP conformed to the expectations of HardyWeinberg equilibrium(P<0.05).(2)There was statistical difference of the genotype frequencies between the MHD group and control group.The frequency of A allele in MHD group was higher than that in control group(P<0.05).(3)There was statistical difference in genotype distribution between LVH group and no LVH group.The frequency of A allele in LVH group was higher than that in no LVH group.There were significant differences in level of FGF23,klotho protein,systolic blood pressure(SBP)and type B natriuretic peptide(BNP)(P <0.05),and the level of klotho protein in LVH group was lower than that in no LVH group,while the levels of FGF23,systolic blood pressure and BNP were higher than those in no LVH Intact parathyroid hormone,creatinine,urea nitrogen,uric acid,blood glucose,triglyceride,total cholesterol,high density lipoprotein and low density lipoprotein.(4)The level of LVMI was positively related with the level of FGF23,SBP and BNP(P<0.05),while negatively related with the level of klotho protein(P<0.05).(5)There was statistical difference on level of LVMI,klotho protein,and diastolic blood pressure between patients with GG genotype and GA+AA genotype(P<0.05).The level of klotho protein in patients with GA+AA genotype was lower than that in GG genotype,while level of the LVMI were higher than those in GG genotype.While no statistical difference was foud on level of FGF23,serum calcium,serum phosphorus,SBP,BNP,creatinine,urea nitrogen and uric acid.(6)Logistic regression analysis showed that GA+AA genotype and systolic blood pressure were independent risk factors of LVH(OR=2.104,95%CI 1.004-4.395,P< 0.05;OR=1.037,95%CI 1.009-1.065,P<0.05),while klotho protein and FGF23,type B natriuretic peptide were not independent factors of LVH.Conclusion: MHD patients with A allele of klotho G-395 A polymorphism may be more likely to develop LVH.A allele,which may be an independent risk factor of LVH.Klotho protein and FGF23 may play roles in the development of LVH in MHD patients.