The Relationship Between Polymorphism Of Osteoprotegerin Gene And Bone Mineral Density In Maintenance Dialysis Patients

Objective:To investigate the single nucleotide polymorphism (SNP) sites of osteoprotegerin(OPG) gene in maintenance hemodialysis patients and healthy controls of Hunan Changsha population, and analyze the relationship between polymorphisms of OPG gene and bone mineral densities (BMD) in maintenance hemodialysis patients, to provide evidence for prediction and prevention in early stage of renal osteodystrophy (ROD).Methods:The genotypes of 48 OPG gene polymorphisms was examined in a population of 112 maintenance hemodialysis patients and 34 healthy controls by matrix assisted laser desorption ionization-time-of-flight mass spectrometer (MALDI-TOF MS) approach. Genomic DNA was extracted from peripheral venous blood cells of the controls and the patients. BMD was measured by dual-energy X-ray absorptiometry(DXA)in the lumbar spine (L2-4)、femoral neck (FN) and 1/3 diatal foream (R+U1/3). Biochemical bone turnover makers such as serum OPG、osteoprotegerin ligand (RANKL)、bone gla protein (BGP) and PTH were also measured. Comparisons of genotype and allele frequency distribution among groups were performed by statistical analysis. BMD and biochemical makers were analyzed among different genotypes of OPG gene and the relationship between SNP and BMD were explored in maintenance hemodialysis patients. Results:(1) The distribution of genotype in Hunan Changsha population did not deviate significantly from the Hardy-Weinberg equilibrium (P>0.05).(2) BMD in patients with different genotypes of OPG gene in two sites of SNP(rs11573928 and rs2073618) were significantly different (P<0.05).①The BMD was lower in patients with AG or GG genotype than those with AA genotype for rs11573928 polymorphism at femoral neck(P<0.05). Patients with genotype GC or GG for rs2073618 had significantly lower lumbar spine BMD than those with CC (P<0.05);②Genotype frequencies of these two polymorphisms did not differ significantly between hemodialysis patients group and healthy control group;③At site of rs2073618, genotype distributions was significantly different between the men and women, the values of genotype CC in male was higher than female, but no statistically significant was observed in BMD and levels of serum OPG、RANKL、BGP and PTH between sexes;④The difference of genotype and allele frequency distribution was significantly different in subgroups divided by different causes of ESRD, it had significantly different BMD in femoral neck and lumbar spine. The patients with hypertension had the lowest BMD⑤Moreover, differences in genotype and allele frequency distribution were not statistically significant in patient groups defined by different ages.(3) At site of rs2073618, frequency of genotypes in hemodialysis patients were as follows:CC (16.1%), GC(30.4%), GG (53.5%). Compared to Hunan Changsha population, the genotype and allele frequencies were statistically significant in the European, while the genotype and allele frequencies were not statistically significant in Japanese and Korean. The distribution of rs2073618 genotypes had race diversity.(4) The age and serum calcium turned out to be associated with osteopenia and osteoporosis in Logistic regression analyses. The rs2073618 polymorphism revealed a trend for predicting osteopenia and osteoporosis in hemodialysis patients (OR=0.265, P=0.016), genotype GG was more frequent in patients with osteopenia and osteoporosis, and it has no relationship with patients’sex、BMI、cause of ESRD、serum phosphate levels and the rs11573928 polymorphism (P>0.05)(5) No statistically significant was observed in levels of serum OPG、RANKL、BGP and PTH among different genotypes of OPG gene in hemodialysis patients (P>0.05)Conclusion:(1) According to our analysis, polymorphisms rs11573928 and rs2073618 in the OPG gene was associated with BMD of hemodialysis patients in Hunan Changsha population.(2) Genotype and allele frequencies of OPG gene polymorphisms were statistically significant in subgroups divided by different causes of ESRD, and the patients with hypertension had the lowest BMD.