open access
The importance of NFκB1 rs4648068 and RUNX2 rs7771980 polymorphisms in bone metabolism of postmenopausal Polish women
, 3, 4, 3, 56, 5, 7, 89
Affiliations- Department of Pharmacology and Phytochemistry, Institute of Natural Fibers and Medicinal Plants, Poznan, Poland
- Department of Histocompatibility with Laboratory of Genetic Diagnostics, Regional Blood Center, Poznan, Poland
- Department of Stem Cells and Regenerative Medicine, Institute of Natural Fibres and Medicinal Plants, Poznan, Poland
- Clinic of Pediatric Orthopedics, Pomeranian Medical University, Szczecin, Poland
- Division of Perinatology and Women’s Diseases, Poznan University of Medical Sciences, Poznan, Poland
- Division of Gynecology and Obstetrics, Podhale Multidisciplinary Hospital, Nowy Targ, Poland
- Independent Laboratory of Invasive Cardiology, Pomeranian Medical University in Szczecin, Poland
- Department of Stem Cells and Regenerative Medicine, Institute of Natural Fibres and Medicinal Plants, Poznan, Poland
- Department of Pharmacology and Pharmacoeconomics, Pomeranian Medical University in Szczecin, Poland
open access
Abstract
Objectives: Osteoporosis is a multifactorial disease that causes a loss of bone density. However, genetic factors play an increasingly important role in its development. To thoroughly understand the molecular mechanisms, polymorphic variants of genes candidate for osteoporosis are still being sought. The aim of our study was to investigate the influence of NFκB1 gene rs4648068 (A>G) and RUNX2 gene rs7771980 (-1025T>C) polymorphisms on the risk of osteoporosis.
Material and methods: A group of 675 postmenopausal Caucasian women (109 women with osteopenia, 333 with osteoporosis and 233 with normal T-score) were examined. The bone mineral density (BMD) at the lumbar spine (L1-L4) was measured by dual energy x-ray absorptiometry (DXA). The analysis of NFκB1 and RUNX2 polymorphisms was performed using real-time PCR method.
Results: Analysis of NFκB1 gene rs4648068 polymorphism showed that the GG genotype was slightly more frequent in the study groups compared to the control group. In the osteoporosis group, patients with the G allele in the genotype have lower bone mineral density values. For the RUNX2 rs7771980 polymorphism, in women with osteopenia we observed an increased incidence of TC heterozygotes compared to the control group (29.40% vs 24.90%, p > 0.05), and in women with osteoporosis, the TT genotype was more common (78.70% vs 73.80%, p > 0.05). No correlation was observed between the genotypes and the clinical parameters.
Conclusions: The analysis showed no significant relationship between the genotypic distribution and the individual clinical parameters. However, it is suggested an association between the rs4648068 polymorphism of the NFκB1 gene and an increased risk of developing osteoporosis.
Abstract
Objectives: Osteoporosis is a multifactorial disease that causes a loss of bone density. However, genetic factors play an increasingly important role in its development. To thoroughly understand the molecular mechanisms, polymorphic variants of genes candidate for osteoporosis are still being sought. The aim of our study was to investigate the influence of NFκB1 gene rs4648068 (A>G) and RUNX2 gene rs7771980 (-1025T>C) polymorphisms on the risk of osteoporosis.
Material and methods: A group of 675 postmenopausal Caucasian women (109 women with osteopenia, 333 with osteoporosis and 233 with normal T-score) were examined. The bone mineral density (BMD) at the lumbar spine (L1-L4) was measured by dual energy x-ray absorptiometry (DXA). The analysis of NFκB1 and RUNX2 polymorphisms was performed using real-time PCR method.
Results: Analysis of NFκB1 gene rs4648068 polymorphism showed that the GG genotype was slightly more frequent in the study groups compared to the control group. In the osteoporosis group, patients with the G allele in the genotype have lower bone mineral density values. For the RUNX2 rs7771980 polymorphism, in women with osteopenia we observed an increased incidence of TC heterozygotes compared to the control group (29.40% vs 24.90%, p > 0.05), and in women with osteoporosis, the TT genotype was more common (78.70% vs 73.80%, p > 0.05). No correlation was observed between the genotypes and the clinical parameters.
Conclusions: The analysis showed no significant relationship between the genotypic distribution and the individual clinical parameters. However, it is suggested an association between the rs4648068 polymorphism of the NFκB1 gene and an increased risk of developing osteoporosis.
Keywords
osteoporosis; polymorphism; NFκB1; RUNX2; postmenopausal women
About this articleTitle
The importance of NFκB1 rs4648068 and RUNX2 rs7771980 polymorphisms in bone metabolism of postmenopausal Polish women
Journal
Issue
Article type
Research paper
Pages
617-623
Published online
2021-04-14
Page views
989
Article views/downloads
562
DOI
Pubmed
Bibliographic record
Ginekol Pol 2021;92(9):617-623.
Keywords
osteoporosis
polymorphism
NFκB1
RUNX2
postmenopausal women
Authors
Anna Bogacz
Aleksandra Gorska
Adam Kaminski
Marlena Wolek
Hubert Wolski
Agnieszka Seremak-Mrozikiewicz
Jaroslaw Goracy
Boguslaw Czerny
References (16)- Sewerynek E, Stuss M. Obowiązujące wskazania do prewencji i leczenia osteoporozy pomenopauzalnej — choroby miliona złamań. Ginekologia i Perinatologia Praktyczna. 2016; 1(2): 45–55.
- Janiszewska M, Kulik T, Dziedzic M, et al. Osteoporoza jako problem społeczny – patogeneza, objawy i czynniki ryzyka osteoporozy pomenopauzalnej. Probl Hig Epidemiol. 2015; 96(1): 106–114.
- Doyle T, Kacmarynski K, Beckett E, et al. Osteoporosis Review. Primary Care Reports. 2019.
- Boroń D, Plewka A, Jędrusik P. Polimorfizm -643C/T genu RANKL i jego związek z osteoporozą u kobiet po menopauzie. Ann Acad Med Siles. 2014; 68(6): 415–423.
- Boyce BF, Xiu Y, Li J, et al. NF-κB-Mediated Regulation of Osteoclastogenesis. Endocrinol Metab (Seoul). 2015; 30(1): 35–44.
- Liu T, Zhang L, Joo D, et al. NF-κB signaling in inflammation. Signal Transduct Target Ther. 2017; 2.
- Zakłos-Szyda M, Budryn G, Grzelczyk J, et al. Evaluation of Isoflavones as Bone Resorption Inhibitors upon Interactions with Receptor Activator of Nuclear Factor-κB Ligand (RANKL). Molecules. 2020; 25(1).
- Witas HW, Wujcicka WI. Genetyczne wyznaczniki osteoporozy. Postępy Biol Komórki. 2007; 34(3): 495–509.
- Novack DV. Role of NF-κB in the skeleton. Cell Res. 2011; 21(1): 169–182.
- Auerkari EI, Suryandari DA, Umami SS, et al. Gene promoter polymorphism of RUNX2 and risk of osteoporosis in postmenopausal Indonesian women. SAGE Open Med. 2014; 2: 2050312114531571.
- Witkowska-Zimny M, Wróbel E, Przybylski J. Najważniejsze czynniki transkrypcyjne procesu osteoblastogenezy. Postępy Biol Komórki. 2009; 36(4): 695–705.
- Iotsova V, Caamaño J, Loy J, et al. Osteopetrosis in mice lacking NF-kappaB1 and NF-kappaB2. Nat Med. 1997; 3(11): 1285–1289.
- Bustamante M, Nogués X, Agueda L, et al. Promoter 2 -1025 T/C polymorphism in the RUNX2 gene is associated with femoral neck bmd in Spanish postmenopausal women. Calcif Tissue Int. 2007; 81(4): 327–332.
- Lee HJ, Koh JM, Hwang JY, et al. Association of a RUNX2 promoter polymorphism with bone mineral density in postmenopausal Korean women. Calcif Tissue Int. 2009; 84(6): 439–445.
- Pineda B, Hermenegildo C, Laporta P, et al. Common polymorphisms rather than rare genetic variants of the Runx2 gene are associated with femoral neck BMD in Spanish women. J Bone Miner Metab. 2010; 28(6): 696–705.
- Vaughan T, Reid DM, Morrison NA, et al. RUNX2 alleles associated with BMD in Scottish women; interaction of RUNX2 alleles with menopausal status and body mass index. Bone. 2004; 34(6): 1029–1036.
