Association Of Apaâ…  Polymorphism Of Vitamin D Receptor Gene With Bone Metabolism In Patients With End-Stage Liver Disease

OBJECTIVE: To investigate the association of Apaâ… polymorphism of vitamin D receptor (VDR) gene with bone metabolism in patients with end-stage liver disease.METHODS: The VDR genotype was determined by polymerase chain reaction -restriction fragment length polymorphism (PCR-RFLP) in 72 patients with end-stage liver diseases and 50 patients with primary osteoporosis (OP) or osteopenia. Bone mineral density (BMD) at lumber spine 1-4 (L1-4) and femoral neck (Neck) were measured by duel-energy X-ray absorptiometry (DXA). The serum level of parathyroid hormone (PTH), osteocalcin (BGP), calcium(Ca), phosphate(P), urinary calcium(uCa) and urinary creatinine(uCr) were also detected in these patients.RESULTS:(1) Frequencies of aa, Aa and AA genotype were 52.78%, 34.72% and 12.50% in the end-stage liver disease group, and 54.00%, 36.00% and 10.00% in the control group, respectively. The allele frequencies of Apaâ… polymorphism were in Hardy-Weinberg equilibrium. There was not significant difference in the frequency distribution of VDR genotype between two groups (P>0.05).(2) Significant association was found between VDR Apaâ… genotype and BMD at L1-4 and Neck (P <0.05) in the group of end-stage liver disease. Compared with aa genotype , AA genotype had significantly higher mean BMD at L1-4 and Neck (P<0.05, P <0.05). Significant association was found between VDR Apaâ… genotype and BMD at L1-4 and Neck (P <0.05,P<0.01) in subgroup of patients with osteoporosis or osteopenia. Compared with aa, Aa genotype had significantly higher mean BMD at L1-4(P<0.05) and compared with Aa and aa, AA genotype had significantly higher mean BMD at Neck(P <0.01,P<0.001). No significant difference was found between Apaâ… genotype and BMD at L1-4 and Neck in the control group.(3) Significant association was found between VDR Apaâ… genotype and the serum level of BGP in the group of end-stage liver disease and its subgroup of osteoporosis or osteopenia. Compared with aa genotype , AA genotype had significantly higher mean serum BGP level (P<0.05). But Apaâ… genotype is not associated with serum level of PTH, Ca, P and uCa/Cr.CONCLUSIONS: Apaâ… genotype polymorphism is associated with BMD and the serum level of BGP in patients with end-stage liver disease. So it is associated with bone metabolism in patients with end-stage liver disease.