Osteoporosis and polymorphisms of osteoprotegerin gene in postmenopausal women – a pilot study (original) (raw)
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International Immunopharmacology, 2015
The aim of the study was to evaluate the frequency of gene polymorphisms OPG −163A/G, −950T/C and 1181G/C, assessing their relations with the clinical parameters of osseous turnover and the degree of postmenopausal osteoporosis. Study design: The study included 800 women of postmenopausal (505) and reproductive (295) age from Poland. The postmenopausal group included women with osteoporosis and osteopenia, as well as healthy individuals. All the women of reproductive age were healthy. The frequency of the tested gene polymorphisms was evaluated within the group where BMD (bone mineral density) was marked and also in the control group. Main outcome measures: The frequencies of the polymorphisms of OPG genotypes in the women were characteristic of the population. Results: OPG −950T/C polymorphism has been associated with body weight and birth weight. OPG 1181G/C and OPG −163A/G polymorphisms have been associated not only with body weight and birth weight, but also with reduced bone density and an increased risk of postmenopausal osteoporosis. Conclusions: Evaluation of the polymorphism − 950T/C of the OPG gene showed that the CC genotype may appear as an increased risk factor for the faster loss of bone mass and the onset of osteoporosis in Polish postmenopausal women. This polymorphism may be a genetic marker that is responsible for the development of osteoporosis. The homozygous genotypes of polymorphisms 1181G/C and −163A/G of the OPG gene may play a role in increased risks of osteoporosis and may be linked to the birth weights of women.
Ginekologia Polska, 2016
Objectives: Recent studies have demonstrated that disorders of bone metabolism, which is regulated by RANK/RANKL/OPG signaling pathway, are the cause of osteoporosis. The aim of the study was to investigate the distribution of genotypes of the RANK 575C>T and RANKL-643C>T polymorphisms and to analyze their relationship with bone parameters in postmenopausal women. Material and methods: A total of 310 postmenopausal Caucasian women (139 with osteoporosis, 107 with osteopenia, and 64 healthy postmenopausal controls) were included. Bone mineral density (BMD) at the lumbar region of the spine (L2-L4) was measured by dual energy X-ray absorptiometry (DXA). Genetic analysis was performed using the PCR-RFLP method. Results: Analysis of the frequency of genotypes and alleles of the RANK 575C>T and RANKL-643C>T polymorphisms did not show any statistically significant differences between the study groups (osteoporosis and osteopenia) and postmenopausal women with normal t-score value (ns). Notably, a significant association between the RANKL-643C>T polymorphism and body mass, such as BMI values in osteoporotic women (p<0.05), was observed. Conclusions: Our results suggest lack of association between the 575C>T RANK polymorphism and the development of osteoporosis. The-643C>T RANKL polymorphism, through its significant influence on body weight and BMI value, may contribute to the development of osteoporosis in postmenopausal women.
Calcified Tissue International, 2004
Although previous studies have established the importance of genetic, hormonal and lifestyle factors separately, the integral role of these factors on bone mass in postmenopausal women is still controversial. We examined the association of the collagen 1alpha-1 gene (COLIA1) and vitamin D receptor gene (VDR) polymorphisms, s-IGF-I, s-25OHD and lifestyle factors with bone mineral density (BMD) in postmenopausal women. We determined anthropometric parameters, lifestyle factors, serum levels of IGF-I and 25OHD, the COLIA1 Sp1 (Mscl) and VDR (Bsml, Taql) polymorphisms by PCR and BMD by dual X-ray absorptiometry in 141 ambulatory postmenopausal Spanish women. There were significant linear correlations between S-25OHD and BMD and between s-IGF-I and BMD. BMD was statistically higher in active subjects. Of the three different polymorphisms, only the COLIA1 Sp1 polymorphism was significantly associated with BMD. In the logistic regression model, the COLIA1 Sp1 polymorphism, S-25OHD, s-IGF-I and physical activity variables were independently associated with osteoporosis. Our study shows that COLIA1 Sp1 polymorphism, S-25OHD and s-IGF-I serum levels and physical activity are independently associated with BMD in postmenopausal Spanish women.
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, 2017
Postmenopausal osteoporosis (PO) has a strong genetic component. Presently, the published evidence on the association between the main single-nucleotide polymorphisms (SNPs) of the receptor activator of nuclear factor-kb ligand (RANKL), osteoprotegerin (OPG) and vitamin D receptor (VDR) and bone mass density (BMD) are scarce, mostly considering Italian population. This study sought to determine whether OPG (rs2073618), RANKL (rs9525641) and the VDR (rs2228570) SNPs were associated with BMD in a sample of 139 North-Italian postmenopausal women. The allelic distribution of rs9525641 in women with PO or osteopenia (OP + OPE group) differed from controls (p < 0.05), suggesting that this allele might confer a greater susceptibility to bone resorption. Concerning rs2228570, CC genotype was associated with OP + OPE women, with a worst total hip BMD. Notably, the combined genotype RANK (CT)-VDR (TT) was significantly associated to spine BMD (p < 0.05). In conclusion, this pilot study ...
Bone, 2007
Bone mass is the single most important risk factor for osteoporotic fractures in the elderly and is mainly influenced by genetic factors accounting for 40-75% of the inter-individual variation. Critical for the bone remodeling process is the balance between the newly discovered members of the tumor necrosis factor ligand and receptor superfamilies, osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand, which mediate the effects of many upstream regulators of bone metabolism. In the present study, we evaluated the impact of sequence variations in the OPG gene on bone mass, bone-related biochemistry including serum OPG and fracture frequency in elderly Australian women. A total of 1101 women were genotyped for 3 different single nucleotide polymorphisms (SNP) within the OPG gene (G1181C, T950C and A163G). The effects of these SNPs and serum OPG on calcaneal quantitative ultrasound measurements, osteodensitometry of the hip and bone-related biochemistry were examined. We found no significant relationship between sequence variations in the OPG gene or serum OPG and bone mass, bone-related biochemistry or fracture frequency. Our findings confirm some recent publications investigating the same SNPs but diverge from others, indicating that generalization of the relationships found in this type of study must be done with caution and signify the importance of determining associations between polymorphisms and osteoporosis in different ethnic groups.
Omentin Polymorphism and its Relations to Bone Mineral Density in Women
Archives of Medical Research, 2015
Background and Aims. 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. The aim of the study was to evaluate frequency of polymorphism 326A/T of gene ITLN-1 and assessment of its relations with the clinical parameters of osseous turnover and degree of postmenopausal osteoporosis. Methods. The study included 800 women at the postmenopausal (505) and reproductive (295) age throughout Wielkopolska region in Poland. 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 BMD was marked and in the control group. Results. The analysis of the polymorphism A326T of gene ITLN-1 showed that in healthy postmenopausal female with genotype AA birth weight, BMD L2eL4 YA (%) and BMD L2eL4 AM (%) were significantly higher (BMDebone mineral density; L2eL4 e lumbar vertebrae no 2, 4; YAepeak adult bone mass; AMeage-matched bone mass). In women with osteopenia BMD L2eL4 YA (%) and BMD L2eL4 AM (%) were significantly higher in women with genotype AA, but BMD L2eL4 was significantly higher in women with genotype TT. In women with osteoporosis with genotype AA Tscore was significantly higher, but BMD L2eL4 and BMD L2eL4 YA (%) were significantly lower in this group. BMD L2eL4 AM (%) was significantly higher in women with AA genotype. Conclusion. In women with osteoporosis and osteopenia homozygous AA genotype may predispose to lower BMD in the lumbar spine.
Calcified Tissue International, 2010
Osteoporosis is a complex disease involving many putative genetic factors. Association analysis of functional SNPs in candidate genes is an important tool for their identification. However, this approach is affected by limited power, population stratification, and other drawbacks that lead to discordant results. Replication in independent cohorts is essential. We performed association analyses of three functional polymorphisms previously associated with bone phenotypes-namely, Ala222Val in MTHFR, Ile1062Val in LRP6, and -13910C[T in LCT-in a cohort of 944 postmenopausal Spanish women, all of them with lumbar spine (LS) bone mineral density (BMD) data and most with femoral neck (FN) BMD and fracture data. We found significant differences between genotypes only for the MTHFR polymorphism and vertebral factures, with an OR of 2.27 (95% CI 1.17-4.38) for the TT vs. CC/ CT genotypes, P = 0.018. We present genotype and allele frequency data for LCT -13910C[T for a Spanish population, where the T allele (conferring lactase persistence) has a frequency of 38.6%. Genotype frequencies were consistent with observed clines in Europe and with the prevalence of lactase nonpersistence. The LCT -13910C[T polymorphism was significantly associated with height and weight, such that T allele carriers were 0.88 cm taller (95% CI 0.08-1.59 cm, P = 0.032, adjusted by age) than CC individuals and TT homozygotes were 1.91 kg heavier than CC/CT individuals (95% CI 0.11-3.71 kg, P = 0.038, adjusted by age). In conclusion, no significant association was observed between the studied polymorphisms and LS BMD or FN BMD in postmenopausal Spanish women, and only MTHFR Ala222Val was associated with vertebral fractures.
Investigating the role of osteoprotegerin gene polymorphic variants in osteoporosis
Russian Open Medical Journal, 2021
In recent genome-wide association studies (GWAS), several polymorphic loci of the osteoprotegerin (OPG) gene were significantly associated with bone mineral density (BMD) and fractures in men over 50 years of age and postmenopausal women. The objective of our study was to search for associations of rs3102735, rs3134069, rs2073617, rs2073618, rs3102734 and rs7844539 of the OPG gene with the risk of osteoporotic fractures and the level of BMD in individual and comorbid conditions in men and women from the Volga-Ural region of Russia. Material and Methods — 828 women and 496 men of various ethnic groups (Russians, Turks) were examined using two-energy x-ray absorptiometry (DEXA) in the femoral neck and lumbar spine. 1324 deoxyribonucleic acid (DNA) samples were genotyped using a fluorescent endpoint genotyping system, after that we searched for associations of these polymorphic loci with fractures and low BMD levels of various localizations. As a result, there was a significant associa...
Human Molecular Genetics, 2000
Bone mineral density (BMD), the major determinant of osteoporotic fracture risk, has a strong genetic component. The discovery that inactivation of estrogen receptor alpha (ERalpha) gene is associated with low BMD indicated ERalpha as a candidate gene for osteoporosis. We have investigated the role of three ERalpha gene polymorphisms [intron 1 PVU:II and XBA:I RFLPs and TA dinucleotide repeat polymorphism 5&amp;#39; upstream of exon 1] in 610 postmenopausal women. There was a strong linkage disequilibrium between intron 1 polymorphic sites and also between these sites and the microsatellite (TA)(n) dinucleotide polymorphism, with a high degree of coincidence of the short TA alleles and the presence of PVU:II and XBA:I restriction sites. No significant relationship between intron 1 RFLPs and BMD was observed. A statistically significant correlation between (TA)(n) repeat allelic variants and lumbar BMD was observed (P = 0.04, ANCOVA), with subjects with a low number of repeats (TA &amp;lt; 15) showing the lowest BMD values. We observed a statistically significant difference in the mean +/- SD number of TA repeats between analyzed women with a vertebral fracture (n = 73) and the non-fracture group, equivalent to 2.9 (95% CI 1.56-5.72) increased fracture risk in women with a low number of repeats (TA &amp;lt; 15). We conclude that in this large population sample the (TA)(n) dinucleotide repeat polymorphism at the 5&amp;#39; end of the ERalpha gene accounts for part of the heritable component of BMD and might prove useful in the prediction of vertebral fracture risk in postmenopausal osteoporosis.