| Objective:To explore the effect of Klotho gene polymorphisms and serum levels of Klotho protein on Chronic Kidney Disease stage5and Bone Mineral DensityMethods:92subjects, including62CKD5patients (B group) and30normal controls(A group) were enrolled in the study. BMD was measured by Dual-energy X-ray absorptiometry (DXA) in patients with CKD5. The patients with CKD5were divided into three groups:normal bone mass(B0group, n=23)、reduced bone mass(B1group, n=22) and osteoporosis(B2group, n=17) according to the standard of osteoporosis recommended by WHO.4ml of venous blood was collected from all subjects. One SNP genotype of Klotho gene was detected by FQ-PCR method and the serum levels of Klotho 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, allele frequencies and Klotho protein, clinical indexes were compared among groups.Results:①The site of G-395A had polymorphism and present three kinds of genotypes of which distribution conformed to Hardy-Weinberg Balance. The frequencies of genotype and allele were following:GG0.674, GA0.272, AA0.054; G0.799, A0.201.②No statistical differences were observed in genotype and allele frequency of G-395A between A and B group (Χ2=0.449, P=0.503; Χ2=1.446, P=0.229).The GA+AA genotype and A allele in B2group were higher than those in B0group (Χ2=5.736, P=0.017, Χ2=7.207, P=0.007). There was no statistical differences in frequency of genotype between B1+B2and B0, while A allele frequency was more higher (Χ2=3.696, P=0.055; Χ2=4.718, P=0.030)③We analyzed the levels of serum Klotho protein in different groups by covariance analysis. The serum Klotho protein in B group were significantly lower than those in A group (F=23.544, P=0.000), there were significant differences in Klotho protein between A group and BO group, B1group, B2group. The protein of B2group were lower than BO group(P=0.049), while no statistical differences existed between B1group and BO group, B2group(P=0.669; P=0.377).④There was no linear correlation between levels of Klotho protein and related clinical indexes in B group.⑤Logistic regression analysis showed:serum levels of Klotho protein was independent determinants for CKD5(OR=0.96,P=0.000) serum Klotho protein, GFR, weight and BMI were all protective factors for BMD in patients with CKD5(OR=0.89,0.58,0.77,0.22, respectively), while Age and GA+AA genotype were both risk factors(OR=3.2,14.74, respectively).Conclusion:①the G-395A site of Klotho gene exists polymorphisms in YangZhou Han Chinese.②the A allele carriers might be genetic risk factors of CKD5complicated by lower BMD.③Reduced serum levels of klotho protein is independent determinants for CKD5and CKD5with lower BMD.④Age, GFR make contribution to reduced BMD and osteoporosis in CKD5patients, while weight and BMI are protective factors. |
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