The effects of vitamin D receptor polymorphism on secondary hyperparathyroidism and bone density after renal transplantation.
Immunosuppresive treatment and secondary hyperparathyroidism (SHPT) are considered among the most important pathogenetic factors for postrenal transplant bone disease. The aim of this study was to investigate the relationships among vitamin D receptor (VDR) gene polymorphism, parathyroid hormone (PTH) levels, and bone density in renal transplant recipients. We enrolled 69 patients (47 men and 22 women; mean age, 47 +/- 11 years) who had undergone kidney transplantation 51 +/- 5 months before. All patients underwent an evaluation of the main biochemical parameters of bone metabolism as well as bone densitometry. VDR alleles were typed by a polymerase chain reaction (PCR) assay based on a polymorphic BsmI restriction site. When the patients were categorized according to the VDR genotype (BB, Bb, and bb), serum creatinine, and the cumulative doses of immunosuppressive drugs were similar across the groups. PTH levels higher than 80 pg/ml were found in 53.6% of the patients, with the highest values being detected in the bb VDR genotype (p < 0.05). PTH was significantly correlated to urinary type I collagen cross-linked N-telopeptide (NTx) values. Bone density was low in the whole population; however, spinal bone density was lower in the bb subgroup (p < 0.02). In the whole population, only PTH (p < 0.05) and body mass index (BMI; p < 0.01) were independent predictors of spinal bone density. When grouping the patients by the VDR gene polymorphism, only PTH continued to be an independent predictor of spinal bone density in the bb allele subgroup (R2 adj. = 0.17). We can conclude that the VDR genotype polymorphism affects bone density of renal transplant recipients via its effects on the severity of SHPT.
D015502:Absorptiometry, Photon; D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D015415:Biomarkers; D015519:Bone Density / Q000235:genetics*; D001842:Bone and Bones / Q000378:metabolism; D002117:Calcitriol / Q000097:blood; D003094:Collagen / Q000652:urine; D024042:Collagen Type I; D015252:Deoxyribonucleases, Type II Site-Specific; D005260:Female; D005272:Femur Neck / Q000737:chemistry; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D007166:Immunosuppressive Agents / Q000009:adverse effects; D007527:Isoenzymes / Q000097:blood; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000601:surgery; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D010455:Peptides / Q000652:urine; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011183:Postoperative Complications; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000502:physiology; D012307:Risk Factors
D015415:Biomarkers; D024042:Collagen Type I; D007166:Immunosuppressive Agents; D007527:Isoenzymes; D010281:Parathyroid Hormone; D010455:Peptides; D018167:Receptors, Calcitriol; C052929:collagen type I trimeric cross-linked peptide; D003094:Collagen; C053864:endodeoxyribonuclease BsmI; D015252:Deoxyribonucleases, Type II Site-Specific; D000469:Alkaline Phosphatase; D002117:Calcitriol