Polymorphism of osteoprotegerin gene and osteoporosis in postmenopausal women

Summary Introduction: Osteoprotegerin (OPG) plays a crucial role in the control of bone resorption through competitive inhibition of receptor activator of nuclear factor κB ligand (RANKL). This process leads to inhibition of osteoclasts differentiation and activity. The aim of the following study was to evaluate the distribution of genotypes of -163A>G and 1181G>C polymorphisms in OPG gene, and analyze their relationship with bone mineral density (BMD) and other parameters of bone turnover in population of Polish postmenopausal women. Material and method: The study included 310 postmenopausal Caucasian women (54,48}8,53 years); 139 women with osteoporosis, 107 with osteopenia and 64 healthy women. Genetic analysis was performed by PCR/RFLP reaction. BMD value was measured by dual energy X-ray absorptiometry (DXA). Results: For -163A>G polymorphism the higher frequency of heterozygotes AG (26.6 vs. 18.7%, ns) and slight overrepresentation of mutated G allel (14,1 vs. 10,9%, ns) in the osteoporosis group was observed. The frequency of recessive CC homozygotes and C alleles of 1181G>C polymorphism did not differ among the investigated groups. The distribution of particular haplotypes of -163A>G and 1181G>C polymorphisms in all subgroups was similar. Correlation between values of investigated parameters of bone turnover and frequency of genotypes of investigated polymorphisms has not been observed. Conclusions: The overrepresentation of heterozygous AG genotype and mutated G allele of -163A>G polymorphism of OPG gene in the group of women with osteoporosis might suggest the significance of this variant in the development of osteoporosis. A more extensive analysis of genetic variants of RANKL/RANK/OPG signal pathways, joint with an investigation of modulated influence of estrogens, TNF-α or several interleukin influencing the development of osteoporosis is necessary.