Parathyroid hormone gene polymorphisms in primary hyperparathyroidism

OBJECTIVE Genetic contributions to bone mineral density (BMD) and bone turnover are well known. In the present study, we analysed the relationship between restriction fragment length polymorphisms of the PTH gene and the development of primary hyperparathyroidism (pHPT) as well as its severity. PATIENTS Seventy-nine pHPT patients and 104 age-matched healthy controls were analysed. DESIGN AND MEASUREMENTS PTH genotypes were determined by polymerase chain reaction and BstBI or DraII restriction fragment length polymorphisms. The presence and absence of BstB I or Dra II restriction sites of the PTH gene were indicated by B and b or D and d, respectively. BMD levels at the lumbar spine and at the radius were measured in all subjects. Serum levels of calcium, phosphorus, alkaline phosphatase and intact PTH were measured in pHPT patients. RESULTS There were no differences in the frequencies of these PTH genotypes between pHPT patients and controls. In control subjects, lumbar BMD was significantly higher in BE genotype than in Bb/bb genotypes, In pHPT patients, there was no difference of BMD between BE and Bb/bb genotypes. In pHPT patients, serum calcium level was significantly higher in those with the BE genotype than Bb/bb genotypes. On the other hand, there was no association between DraII polymorphism and BMD in both controls and pHPT patients, but serum intact PTH level was significantly higher in DD genotype than Dd/dd genotype in pHPT patients. Moreover, serum levels of ALP and intact PTH were significantly higher in the PTH BBDD haplotype, compared to those in haplotypes other than BBDD. CONCLUSIONS The present study suggests that the BstBI polymorphism of PTH gene is closely related to bone mineral density and that PTH gene polymorphisms do not seem to affect the development of primary hyperparathyroidism but may relate to the severity of primary hyperparathyroidism.