THE ROLE OF VITAMIN-D-RECEPTOR GENE ALLELES IN THE SECONDARY HYPERPARATHYROIDISM OF HEMODIALYSIS-PATIENTS

It has been suggested that bone mass is genetically associated with an allelic variation in the 1,25-dihydroxyvitamin D receptor (VDR), with the b allele associated with higher bone density than the B allele, W e investigated the association between VDR genotype, bone mineral dens ity (EMD) and biochemical (Ca, P, iPTH) profiles in 30 nondiabetic dia lysis patients, treated with i.v. calcitriol, The individual genetic p attern for VDR was evaluated by DNA extraction followed by PCR amplifi cation and digestion with restriction enzyme of the DNA sequence flank ing the BsmI site, BMD was measured by dual energy Xray absorptiometry (DEXA). Mean BMD (with 95% confidence interval) in the bb allele grou p of patients was 0.85 (0.70 - 1.01 g/cm(2), lower but not significant ly different from Bb allele patients: 1.01 (0.91 - 1.10) g/cm(2), or t he BB allele group: 1.03 (0.83 - 1.22) g/cm(2). One year later, BE and Bb patients underwent a second BMD measurement: BE patients treated w ith calcitriol maintained near-normal BMD, whereas BE genotype patient s not receiving calcitriol presented a rapid decline in BMD, while Bb genotype subjects showed no real changes, Before treatment, mean (+/-S D) iPTH serum levels were higher in the bb group (465+/-112 pg/ml) tha n in the BE patients (252+/-49 pg/ml); after 48 months of calcitriol t herapy, the former showed a 59% reduction in their iPTH concentrations , while the latter had a nonsignificant decline, Bb patients behaved s imilarly to bb subjects. The efficacy of the therapeutic approach, esp ecially in patients who share the stress of uremia and an unfavourable genetic pattern, was substantiated by the present study.