Associations of polymorphisms in the vitamin D receptor gene (BsmI and FokI) with bone mineral density in postmenopausal women in Malta

Abstract

Previous studies have suggested that variations in the vitamin D receptor (VDR) gene are related to bone mineral density (BMD). In this study, the T-->C transition in the start codon and the G-->A polymorphism at the 3' end of the VDR gene, identified by endonucleases FokI and BsmI, respectively, were analysed and correlated with BMD in postmenopausal Maltese women ( n=104). Genotype frequencies observed for the VDR start codon polymorphism (SCP) were CC: 60.4%; CT: 30.7% and TT: 8.9%, while those observed for the 3' in this study were GG: 16.4%; GA: 51.9%; AA: 31.7%. In postmenopausal women, both lumbar and femoral BMD were observed to be highest in CC homozygotes for the FokI genotype and in GG homozygotes for the BsmI genotype, although in both groups the difference between the genotypes was not statistically significant, even after adjusting BMD for age, BMI and years since menopause. No evidence of linkage disequilibrium between the two alleles was observed.

Vitamin D status in relation to obesity, bone mineral density, bone turnover markers and vitamin D receptor genotypes in healthy Saudi pre- and postmenopausal women

“…No differences were obtained in BMD values or BTMs among the genotypes; which is similar to previous reports [63][64][65][66][67] and controlling for serum 25(OH)D and/or menopausal status did not influence these findings.…”

“…In the present study, high prevalence of vitamin D insufficiency in both pre-and postmenopausal women was associated with significant inverse correlations between serum 25(OH)D levels and that of intact PTH and then with serum magnesium; the latter correlations were probably directed by secondary hyperparathyroidism evident in about 22% of the studied women with serum 25(OH)D<50 nmol/ L. Several studies have demonstrated that serum 25(OH)D to be inversely related to serum PTH [62][63][64], and that hyperparathyroidism secondary to vitamin D deficiency may precipitate into cortical bone loss leading to enhanced bone turnover [1][2][3]. Moreover, serum 25(OH)D exhibited positive correlations with BMD values of the lumbar spine (L1-L4) and more significantly with that of neck femur even after adjustment for age and BMI; the latter observations were similar to that observed in other studies in both young [68][69][70][71][72] and elderly [9,73] women.…”

Linkage to chromosome 11p12 in two Maltese families with a highly penetrant form of osteoporosis

“…These families were recruited from the Department of Obstetrics and Gynaecology, St Luke's Hospital, Malta and selected from probands that already participated in previous association studies. 17,18 These two probands were observed to be severely osteoporotic according to WHO criteria (t-scoreoÀ2.50), where both probands had t-scores of À3.50, were relatively young in age when diagnosed (50 and 55 years, respectively) and have a known family history of osteoporosis. A total of 27 family members were recruited, nine of whom came from pedigree 1 and 18 from pedigree 2 ( Table 1).…”

“…Sequence variants identified were analysed in all family members and a cohort of unrelated postmenopausal women, 17,18 either by direct sequencing or by restriction fragment length polymorphism (RFLP). PCR products (10 ml) were digested using appropriate restriction enzymes according to the manufacturer's instructions (New England Biolabs, Beverly, MA, USA).…”

Lack of association of vitamin D receptor gene polymorphisms/haplotypes in Sjögren’s syndrome

“…Three polymorphisms, BsmI and ApaI (both in intron 8), and TaqI (in exon 9) have been identified at the 3' end of the gene. Recent studies have reported that allelic variations of the VDR gene polymorphisms might be associated with a variety of diseases, including osteoarthritis, diabetes, cancer, cardiovascular diseases, tuberculosis, virus infections, urinary stones, periodontitis [13][14][15][16][17][18]. These findings suggest that allelic variations of the VDR gene may partially represent a genetic component associated with the development of autoimmune diseases.…”