1. THE IMPORTANCE OF GENE POLYMORPHISMS IN RANKL/RANK/OPG PATHWAY IN ETIOLOGY OF POSTMENOPAUSAL OSTEOPOROSIS
Adam Kamiński1, Karolina Dziekan1, Hubert Wolski2, Radosław Kujawski1, Anna Bogacz1,3, Marcin Ożarowski1,4, Bogusław Czerny1,5, Małgorzata Górska-Paukszta1, Agnieszka Seremak-Mrozikiewicz1,2
1Institute of Natural Fibres and Medicinal Plants, Plewiska, Poland 2Division of Perinatology and Women’s Diseases, Poznan University of Medical Sciences, Poznan, Poland 3Department of Clinical Pharmacy and Biopharmacy, University of Medical Sciences, Poznan, Poland 4Department of Pharmaceutical Botany and Plant Biotechnology, University of Medical Sciences, Poznan, Poland 5Department of General Pharmacology and Pharmacoeconomics, Pomeranian Medical University, Szczecin, Poland D
INTRODUCTION
Osteoporosis is a serious metabolic disorder in advanced age with decreased bone mineral density with a significant role of hormonal, environmental and genetic factors. In recent years it has been noted that the processes of growth, maturity, segregation and differentiation of osteoclasts are synchronized and modulated by many factors, in which the key role could play the signal pathway that is directly involved in bone resorption. Currently it is though that in this trail the receptor activator of nuclear factor kappa B (RANK), its ligand (RANKL – receptor activator of nuclear factor - B ligand) and osteoprotegerin (OPG) are involved.
It seems that dynamic steadiness between RANKL/RANK and OPG activities determines the regulation of differentiation and activation of osteoclasts, thus significantly affects the metabolism of bone tissue. The RANKL/RANK/OPG trail is directly involved into the proliferation and apoptosis of osteoclasts. The disturbances in RANKL/RANK/OPG system can be major part of postmenopausal osteoporosis etiology. Moreover it has been shown that genes encoding RANKL/RANK/OPG system are closely involved in osteoporosis development.
The aim of this study was to investigate the distribution of genotypes of OPG (163A>G, -245T>G, -950T>C, 1181G>C), RANK (575C>T) and RANKL (-643C>T) polymorphisms in the group of postmenopausal women and to determine the connection of examined genetic variants with parameters of the bone turnover and progresses of osteoporosis.
However, the TT genotype and T allele of -643C>T polymorphism appeared more frequent in the group with osteoporosis and osteopenia compared to healthy women.
We also suggest lack of correlation of the -245T>G, -950T>C and 1181G>C polymorphisms of OPG gene and RANK 575C>T polymorphism with the occurrence of osteoporosis [Tab. 1.].
Tab. 1. The frequency of occurrence of polymorphisms of the OPG, RANK, RANKL genotypes in women with osteoporosis, osteopenia, healthy in postmenopausal and in reproductive age.
Genotype
Women with osteopenia
Women with osteoporosis
Women with normal T-score
Women in reproductive age
Observed value n (%)
OPG -163A/G AA
83 (76,9%)
100 (72,5%)
51 (81,0%)
158 (73,1%) AG
22 (20,4%)
37 (26,8%)
11 (17,5%)
53 (24,5%) GG
3 (2,8%)
1 (0,7%)
1 (1,6%)
5 (2,3%)
OPG -950T/C TT
38 (36,9%)
41 (30,8%)
15 (25,4%)
85 (29,3%) TC
42 (40,8%)
56 (42,1%)
28 (47,5%)
143 (49,3%) CC
23 (22,3%)
36 (27,1%)
16 (27,1%)
62 (21,4%)
RANK 575C/T
12 (20,0%)
15 (34,1%)
3 (11,1%)
46 (28,8%) CT
34 (56,7%)
21 (47,7%)
19 (70,4%)
82 (51,2%)
14 (23,3%)
8 (18,2%)
5 (18,5%)
32 (20,0%)
RANKL -643C/T
13 (18,6%)
11 (23,4%)
10 (31,3%)
28 (17,5%)
39 (55,7%)
26 (55,3%)
20 (62,5%)
94 (58,8%)
18 (25,7%)
10 (21,3%)
2 (6,2%)
38 (23,7%)
MATERIAL AND METHODS
The study included 310 postmenopausal Caucasian women (139 women with osteoporosis, 107 women with osteopenia and 64 healthy women) (Fig. 1.). The bone mineral density (BMD) at the lumbar spine (L1-L4) was measured by dual energy x-ray absorptiometry (DXA). Genetic analysis was performed using PCR-RFLP method.
Fig. 1. The characteristics of women in postmenopausal age
CONCLUSIONS
These findings could suggest a participation of the OPG -163A>G polymorphism in osteoporosis development. Moreover, the RANKL -643C>T polymorphism may have a significant influence on body weight and BMI in postmenopausal women with osteoporosis.
REFERENCES
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RESULTS
The results showed a higher frequency of heterozygotes AG genotype and mutated G allele of the -163A>G polymorphism in OPG gene in women with osteoporosis. Analysis of the frequency of genotypes and alleles of RANK and RANKL polymorphisms showed no statistically significant differences between study groups.