The Effect Of Klotho Gene Polymorphisms And Serum Levels Of Klotho Protein On Chronic Kidney Disease Stage 5 With Calcium And Phosphorus Metabolism

Objective:To explore the effect of Klothogene polymorphisms and serum levels of Klotho protein on Chronic Kidney Disease stage 5 with calcium and phosphorus metabolism.Methods:280 subjects,including 200 CKD5 patients(The non dialysis group included 102 patients,59 cases of hemodialysis group,and 39 cases of Peritoneal dialysis group)and 80 normal controls were enrolled in the study.4 ml of venous blood was collected from all subjects.One SNP genotype ofKlotho gene was detected by FQ-PCR method and the serum levels of protein were tested using enzyme linked immuno sorbent assay(ELISA)in all subjects.Meanwhile,other related clinical and biochemical parameters were also evaluated in patients with CKD5.The genotypes frequencies and allele frequencies were compared among groups.Klotho protein levels werecompared among eachsubgroup of CKD5,and analyzedthe correlation between the Klotho protein and the calcium and phosphorus metabolism related indexes.Results:(1)The site of G-395A had polymorphism and present three kinds of genotypes of which distribution conformed to Hardy-Weinberg Balance.(2)Statistical differences were observed in genotype and allele frequency of G-395A between CKD5 and control group(P<0.05).Statistical differences were observed in genotype and allele frequency of G-395A between CKD and control group(P<0.05).The GA+AA genotype and A allele in B group were higher than those in A group(P<0.05).(3)The levels of Klotho proteinin CKD stage5 were found to be ignificantly lower compared with normal control group(P<0.01).We analyzed thatthe lever of serum calciumhad statistical differences(P<0.05)among different groups(BO、B1 and B2).The serum phosphorus,serum Klotho protein and FGF23 had no statistical differences between B0 group,B1 groupand B2 group.(4)There were significants differences in serum calcium and phosphorus between GG and GA+AA group in CKD5 non hemodialysis patients(P=0.034,P=0.027).There was significant difference in serum calcium between GG and GA+AA group in hemodialysis and peritoneal dialysis patients(P=0.009;P=0.002).Among each subgroup of CKD5,there were no differences in serum Klotho protein and FGF23 between GG and GA+AA group.(5)The levels of Klotho protein were negatively correlated with FGF23(P<0.01;P<0.01;P==0.001).The levels of Klotho proteinwere positively correlated withserum calcium(r0=0.449,P0<0.01;r1=0.394,Pi=0.02)and negatively correlated with serum phosphorus(r0=-0.624,P0<0.01;ri=-0.406,P1=0.001)in BO group and B1 group.Klotho levels were positively correlated with iPTH(r=-0.335,P=0.037)in peritoneal dialysis patients.(6)Logistic regression analysis showed:GA+AA genotype(OR=5.962,P<0.01),serum levels of Klotho protein(OR=0.892,P=0.015)and FGF23(OR=1.115,P<0.01)were independent determinants for CKD5 with calcium and phosphorus metabolism.Conclusion:(1)The G-395A site of Klotho gene exists polymorphisms in JiangSu Han Chinese.The frequency ofGA+AAgenotype was higer than GG genotype.(2)The GA + AA genotype may be related to CKD5 with calcium and phosphorus metabolism.(3)Klotho and FGF23 may be related with the mineral metabolic disorder in chronic kidney disease.Klotho is a protective factor,while FGF23 is an independent risk factor.