Relationship Between Klotho Gene Polymorphisms And Severe Secondary Hyperparathyroidism

Objective:To evaluate the effect of klotho gene polymorphisms on severe secondary hyperparathyroidism in the maintenance hemodialysis patients and the effect of parathyroidectomy on calcium and phosphorus metabolism.Methods:167 patients with calcium and phosphorus metabolism disorders for long-term hemodialysis treatment were enrolled in the group B(MHD),60 normal controls were enrolled for group A in the study.87 patients had undergone parathyroidectomy for severe secondary hyperparathyroidism were included in the group Bland 80 patients with Mild-to-moderate secondary hyperparathyroidism only treated with medicines were group B2.Blood samples were collected from all subjects,PCR amplification was used to detect the single nucleotide polymorphism of the Klotho gene at G-395A by one-generation sequencing and enzyme linked immuno sorbent assay(ELISA)was used for serum levels of klotho protein and FGF23.Meanwhile,other related clinical and biochemical parameters were also evaluated in all patients.The genotypes frequencies and allele frequencies were compared between group A and group B.The effects of parathyroidectomy on calcium and phosphorus metabolism and Klotho protein and FGF23 were detected.Results:?The site of G-395A had polymorphism and present for genotype GG,GA,and AA,the distribution of genotypes conformed to Hardy-Weinberg Balance and had a certain group representativeness.?Statistical differences were observed in genotype and allele frequencies of G-395A between MHD 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).?There was no significant difference in the genotype of G395A between group B1(serious secondary hyperparathyroidism)and group B2(mild-to-moderate secondary hyperparathyroidism)(P>0.05).A allele in group B1 was higher than that of group B2(P<0.05).? Logistic regression analysis showed:A allele was independent determinant for severe secondary hyperparathyroidism(OR=0.462,95%CI 0.213-0.922,P=0.029).?Pearson correlation analysis showed:FGF23 was positively correlated with serum phosphorus,calcium-phosphorus product and PTH(r=0.314,P?0.000;r=0.292,P?0.000;r=0.389,P?0.000).Klotho levels were negatively correlated with serum phosphorus,calcium-phosphorus product and PTH(r=-0.447,P?0.000;r=-0.389,P?0.000;r=-0.355,P?0.000).?The effects of parathyroidectomy on patients in group B:serum phosphorus,calcium-phosphorus product,PTH,FGF23 in group B1(surgical group)were lower than those in group B2(non-surgical group)(P<0.05),Calcium,hemoglobin and albumin in group B1 were higher than those in B2 group(P<0.05).No significant difference of Klotho level was observed in group B1 and group B2(P>0.05).Conclusion:?the G-395A site of Klotho gene exists polymorphisms in YangZhou Han Chinese.?The A allele carriers might be genetic risk factors for ESRD and MHD with severe SHPT.?Klotho protein may be a protective factor for MHD with SHPT and FGF23 may be a risk factor for MHD with SHPT.?Mineral metabolism disorders in the MHD patiens complicated with severe SHPT were improved after parathyroidectomy,the expression of klotho protein was not change.The reduce of FGF23 after parathyroidectomy might association with better outcomes of MHD patients.