Study On Klotho Gene Polymorphism In Patients With End Stage Renal Disease

The prevention and treatment has lagged behind because of medicalresearches on occurrence and development of renal disease unextensivelydown to the level of the gene. Patients attacted by kidney diseases inevitablyprogressed to end-stage kidney disease (ERSD) and needed to have dialysis ora kidney transplant.Patients with ESRD disease mortality is very high andmany patients die of cardiovascular complications. Several biologicalprogresses including renal fibrosis,calcium and phosphorus metabolicregulation, inhibition of oxidative stress participated in ESRD,cardio-cerebralvascular disease,metabolic syndrome and osteoporosis,but only therelationship between Klotho gene polymorphisms and ESRD had not beexplored at home. So, in this paper, the relations between the Klotho gene andESRD were investigated including reported SNPs rs9536314, rs9527025,rs2149860with the ESRD susceptibility and its complications.Objective: To investigate the association of the polymorphisms of partialfragment of Klotho gene with the ESRD susceptibility and its complications.Method: The case-control study was performed in the Han populationconsisting of215patients with ESRD and170general healthy controls. Thegenomic DNA samples were purified from the whole peripheral blood andPCR-SBT was used for the detection of Klotho gene1165bp fragment SNPsincluding reported SNPs rs9536314, rs9527025, rs2149860that involvedgenotype frequency.Meanwhile we tested the levels of serum biochemicalindicators and intima-media thickness of carotid artery,then each index ofgenotype was compared. The genotype frequency of rs9536314, rs9527025,rs2149860among different groups that divided by Cardiovascular disease,Cerebrovascular disease, Restless legs syndrome,Diabetic nephropathy,Hepatitis B and Hepatitis C. were compared. Results:1By our investigation,the major proportion of original disease of ESRDwere attributed to chronic glomerulonephritis46.1%(99/215), followed bydiabetic nephropathy21.4%(46/215),and then hypertensive nephropathy11.2%(24/215); The prevalence rate of disorders of calcium and phosphorusmetabolism in patients with ESRD was86.7%while73.1%ESRD patientswere attacted by hyperparathyroidism. All ESRD patients had thickerintima-media thickness of carotid artery; The case rate of cardiovasculardisease was detected in33.3%while the case rate of restless leg syndrome was58.6%. Approximately the prevalence rate of cerebrovascular disease was58.6%. The prevalence rate of hepatitis C infection(11.8%) was significantlyhigher than that of hepatitis B(7%).Klotho244, Klotho424, Klotho430,Klotho562SNPs were newly discovered in this paper.2The results of PCR-SBT suggested a heterozygote of rs9536314(TG)and rs9527025(GC) existed in the case group and the control grouprespectively that is different from20%~31%heterozygous of Caucasians inforeign research[3],the rest were homozygous (TT,GG). The heterozygoteadvantage of rs2149860(AG) was obvious in both the case group and thecontrol group and the genotype frequency of AA was more than that ofGG..The control group had two heterozygous of Klotho424(TG),the otherswere homozygous(GG).A heterozygote of Klotho244(TG) and Klotho562(GC)existed in the case group and the control group respectively,the rest werehomozygous (GG,TT). Only a heterozygote(GA) of Klotho430was found incase group. The SNPs of Klotho including rs9536314,rs9527025,rs2149860,Klotho244, Klotho424,Klotho430and Klotho562between the two groupswere not statistically different.3In case control studies exploring the association of cardiovasculardisease,cerebrovascular disease, restless legs syndrome or diabeticnephropathy in ESRD patients of sustaining hemodialysis, SNPs of Klothoincluding rs9536314,rs9527025,rs2149860, Klotho244, Klotho424,Klotho430and Klotho562were genotyped and no evidence suggested the relationships. 4In case control studies exploring the association of hepatitis B orhepatitis C infections in ESRD p atients of sustaining hemodialysis,SNPs ofKlotho including rs9536314,rs9527025,rs2149860, Klotho244, Klotho424,Klotho430and Klotho562were genotyped and no evidence suggested therelationships.5In case control studies exploring the association of the levels of serumbiochemical indicators and intima-media thickness of carotid artery in ESRDpatients of sustaining hemodialysis, rs2149860site was genotyped and noevidence suggested the relationships.6There was no relationship between Intima-media thickness of carotidartery and Cardio-cerebral vascular disease of ESRD patients.Conclusion:1In China, Chronic glomerulonephritis, diabetic nephropathy,hypertensive nephropathy, hereditary nephropathy (polycystic kidney),obstructive nephropathy, other diseases were listed as the causes of ESRD.Although ESRD can occur at any age, its onset was mostly between the ages40and70.2There was polymorphism in Klotho gene because of racial differencesand no evidence suggested the relationship between the Klotho genepolymorphism and ESRD in the Northern Han Chinese cohort.3The statistical results suggested that the Klotho gene polymorphismwere not associated with cardiovascular disease,cerebrovascular disease,restless legs syndrome and diabetic nephropathy in the Northern Han Chinesecohort.4The prevalence rate of hepatitis C was significantly higher than that ofhepatitis B,the Klotho gene polymorphism were not associated with hepatitisC and hepatitis B in the Northern Han Chinese cohort.5The prevalence rate of disorders of calcium and phosphorus metabolismin patients with ESRD was86.7%while73.1%of ESRD patients wereattacted by hyperparathyroidism.All ESRD patients had thicker intima-mediathickness of carotid artery,but the Klotho gene polymorphism were not associated with vascular calcification,calcium and phosphorus metabolism andhyperparathyroidism in the Northern Han Chinese cohort.6There was no relationship between intima-media thickness of carotidartery and Cardio-cerebrovascular diseases in the Northern Han Chinesecohort.