1. ANALYSIS OF VITAMIN D RECEPTOR POLYMORPHISM AND ITS RELATION TO MINERAL BONE DENSITY IN THE PATHOGENESIS OF OSTEOPOROSIS
Bogusław Czerny1,2, Izabela Uzar2, Dariusz Boroń3, Anna Bogacz1,4,Karolina Dziekan1, Aleksandra Kowalska1, Radosław Kujawski1, Agnieszka Seremak-Mrozikiewicz1,5, Adam Kamiński1
1Institute of Natural Fibres and Medicinal Plants, Plewiska, Poland 2Department of General Pharmacology and Pharmacoeconomics, Pomeranian Medical University, Szczecin, Poland 3Department of Histology and Embryology, Medical University of Silesia, Zabrze, Poland 4Department of Clinical Pharmacy and Biopharmacy, University of Medical Sciences, Poznan, Poland 5Division of Perinatology and Women’s Diseases, Poznan University of Medical Sciences, Poznan, Poland D
INTRODUCTION
Postmenopausal osteoporosis is the most common metabolic bone disease of strong genetic origin with population variability determined by the interaction of genetic and environmental factors. Recognition of different genetic variants underlying development of osteoporosis would make it possible to administer individual symptomatic treatment as well as early prophylactics of osteoporosis.
Vitamin D receptor (VDR) belongs to the nuclear receptors, activated by a ligand and performing as transcription factors. Initially, VDR polymorphism was analysed in disease associated with bone metabolism, yet the studies were gradually extended to comprise the role of vitamin D3 receptor in the pathogenesis of other disorders, including the neoplastic diseases.
A dependency was proved to exist between the mineral density of bones and the variants of the VDR gene, coding the receptor protein for vitamin D.
It is known that the effect of polymorphism on bone mineral density is not explicit and may interfere with other factors of both genetic and environmental nature. This turned the scientists’ efforts towards effects brought by polymorphisms within the VDR gene, commencing a new era in studies aimed at identification of genes involved in pathogenesis of osteoporosis.
The aim of the study was to evaluate the frequency of polymorphism 283G>A of the vitamin D3 VDR gene receptor and assessment of its relations with the clinical parameters of osseous turnover and degree of postmenopausal osteoporosis.
RESULTS
The obtained test results pointed to correlation of polymorphism VDR 283G>A with the BMD scores for the lumbar vertebrae in women with osteopenia and osteoporosis, therefore the ones at risk of fractures.
Vitamin D receptor (VDR) polymorphism correlated with reduced BMD values.
The frequency of occurrence of polymorphism of the VDR 283G>A genotypes in women with osteoporosis, osteopenia, healthy in postmenopausal and in reproductive age.
Genotype VDR 283G/A
Women with osteoporosis
Women with osteopenia
Women with normal
T-score
Women in reproductive age
Observed value n (%) GG
56 (20,1%)
12 (11,4%)
11 (19,0%)
51 (17,4%) AG
121 (43,5%)
48 (45,7%)
22 (37,9%)
113 (38,9%) AA
101 (36,3%)
45 (42,9%)
25 (43,1%)
128 (43,7%)
Recently, some more reports have confirmed the genetic background of bone mineral density. Even if information on the effect of a given gene or genes are contradictory, the scientists do agree that bone mineral density depends in 75– 80% on the genetic factors.
So far, no single gene was found to prevail over others in the determination of bone mineral density. It is most probably a multi-gene relation. Among the number of genes, tested most frequently was the vitamin D receptor gene or genes coding collagen.
For such reasons, this study chose the gene coding the receptor for active vitamin D metabolites recognized as one with polymorphism likely to affect the osseous tissue density in the patients.
MATERIAL AND METHODS
The study included 800 women at the postmenopausal (505) and reproductive (295) age from Caucasian population. The postmenopausal group included women with osteoporosis and osteopenia and the healthy ones. Women at the reproductive age were healthy. Frequency of the tested gene polymorphism was evaluated in the group where bone mineral density (BMD) was marked and in the control group.
Analysis of polymorphism was performed by real-time PCR using HybProbe probes while BMD was measured by dual-energy X-ray absorptiometry (DEXA) method.
The characteristics of women in postmenopausal age
CONCLUSION
Polymorphism 283G>A of the vitamin D3 receptor gene has been proved to be the genetic factor of postmenopausal osteoporosis. The polymorphism mentioned above has been proved to be a factor of mineral bone density changes of women.
REFERENCES
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