ÖZET
Amaç:
Reseptör aktivatör nükleer faktör-B ligandı (RANKL) ve osteoprotegerinin (OPG) kemik yeniden modelleme ve osteoporozda önemli bir rolü olduğu gösterilmiştir. Bu çalışmada, Endonezya menopoz sonrası kadınlarda düşük kemik mineral yoğunluğu (KMY) ile RANKL ve OPG genlerinin polimorfizmleri (sırasıyla TNFSF11 ve TNFRSF11B) arasındaki ilişkinin araştırılması amaçlanmıştır.
Gereç ve Yöntem:
Elli - altmış beş yaş arası 60 postmenopozal kadın uygun bulundu. KMY, çift-enerjili X-ışını absorpsiyometrisi kullanılarak ölçülmüştür. TNFSF11 ve TNFRSF11B’nin genotipleri polimeraz zincir reaksiyonu-kısıtlama fragman uzunluğu polimorfizmleri ve DNA dizileme yöntemleri ile elde edildi. TNFSF11’den (-290C> T, -643C> T, -693G> C) ve TNFRSF11B’den (163A>G, 950T>C, 1181G>C) üç tek nükleotid polimorfizmleri (SNP) seçildi. Allel dağılımı ile KMY arasındaki ilişki ki-kare veya Fischer kesin testi kullanılarak hesaplandı. Kemik bölgelerindeki tüm SNP’leri ve BMD’yi analiz etmek için çoklu lojistik regresyon kullanıldı. Anlamlılık p<0,05 olarak ayarlandı.
Bulgular:
Çoğu birey daha düşük KMY’ye (%83,3) sahipti. Sağlıklı ve düşük KMY arasındaki bireylerin özellikleri karşılaştırılabilir bulundu (hepsi p>0,05). TNSSF11 ve TNFRSF11B’de genotiplerin ve allellerin sağlıklı ve düşük KMY’ler arasındaki dağılımı anlamlı olarak farklı değildi (hepsi p>0,05). Tüm kemik bölgelerinde TNFSF11 ve TNFRSF11B’nin SNP’leri ile KMY arasında ilişki yoktu (hepsi p>0,05).
Sonuç:
Bu çalışma, 50-65 yaşlarındaki Endonezyalı postmenopozal kadınlarda TNFSF11 ve TNFRSF11 gen polimorfizmlerinin BMD ile ilişkili olmadığını düşündürmektedir.
References
1
Wade SW, Strader C, Fitzpatrick LA, Anthony MS, O’Malley CD. Estimating prevalence of osteoporosis: examples from industrialized countries. Arch Osteoporos 2014;9:182.
2
Mithal A, Dhingra V, Lau E. The Asian Audit. Epidemiology, costs and burden of osteoporosis in Asia 2009. International Osteoporosis Foundation. https://www.iofbonehealth.org/sites/default/files/PDFs/Audit%20Asia/Asian_regional_audit_2009.pdf
3
Population Statistics for Seniors 2013, Central Bureau of Statistics, Jakarta-Indonesia.
4
Data And Osteoporosis Disease Condition in Indonesia. Infodatin Data and Information Center Ministry of Health RI. 2015. https://www.depkes.go.id. 26th April 2017.
5
Weitzmann MN, Pacifici R. Estrogen deficiency and bone loss: an inflammatory tale. J Clin Invest 2006;116:1186-94.
6
Raggat LJ, Partridge NC. Cellular and molecular mechanisms of bone remodelling. J Biol Chem 2010;285:25103-8.
7
Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature 2003;423:337-42.
8
Liu C, Walter TS, Huang P, Zhang S, Zhu X, Wu Y, et al. Structural and functional insights of RANKL-RANK interaction and signaling. J Immunol 2010;184:6910-9.
9
Martin TJ, Sims NA. How cells communicate in the bone remodelling process. J Korean Endocr Soc 2010;25:1-8.
10
Seremak-Mrozikiewicz A, Barlik M, Drews K, Bogacz A, Tatuśko J, Piotrowska A, et al. The genetic variants of RANKL/RANK/OPG signal trial in postmenopausal women with osteopenia and osteoporosis. Arch perinatal Med 2011;17:72-80.
11
Klein-Nulend J, Bakker AD, Bacabac RG, Vatsa A, Weinbaum S. Mechanosensation and transduction in osteocytes. Bone 2013;54:182-90.
12
Roshandel D, Holliday KL, Pye SR, Boonen S, Borghs H, Vanderschuren D, et al. Genetic variation in the RANKL/RANK/OPG signaling pathway is associated with bone turnover and bone mineral density in men. J Bone Miner Res 2010;25:1830-8.
13
Takács I, Lazáry Á, Kósa JP, Kiss J, Balla B, Nagy Z, et al. Allelic variations of RANKL/OPG signaling system are related to bone mineral density and in vivo gene expression. Eur J Endocrinol 2010;162:423-31.
14
Cheung CL, Xiao SM, Kung AWC. Genetic epidemiology of age-related osteoporosis and its clinical applications. Nat Rev Rheumatol 2010;6:507-17.
15
Zheng H, Wang C, He JW, Fu WZ, Zhang ZL. OPG, RANKL, and RANK gene polymorphism and the bone mineral density response to alendronate therapy in postmenopausal Chinese women with osteoporosis or osteopenia. Pharmacogenet Genomics 2016;26:12-9.
16
Wolski H, Drews K, Bogacz A, Kamiński A, Barlik M, Bartkowiak-Wieczorek J, et al. The RANKL/RANK/OPG signal trail: significance of genetic polymorphisms in the etiology of postmenopausal osteoporosis. Ginekol Pol 2016;87:347-52.
17
Boroňová I, Bernasovská J, Mačeková S, Petrejčíková E, Tomková Z, Kľoc J, et al. TNFRSF11B gene polymorphisms, bone mineral density, and fractures in Slovak postmenopausal women. J Appl Genetics 2015;56:57-63.
18
Sassi R, Sahli H, Cheour E, Sellami S, El Gaaied ABA. -643C > T RANKL gene polymorphism is associated with osteoporosis in Tunisian postmenopausal women. Climacteric 2017;20:374-8.
19
Blake GM, Fogelman I. The role of DXA bone density scans in the diagnosis and treatment of osteoporosis. Postgrad Med J 2007;83:509-17.
20
Millar SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988;16:1215.
21
Mencej S, Prezelj J, Kocijancic A, Ostanek B, Marc J. Association of TNFSF11 gene promoter polymorphisms with bone mineral density in postmenopausal women. Maturitas 2006;55:219-26.
22
Mencej S, Albagha OME, Prezelj J, Kocjan T, Marc J. Tumor necrosis factor superfamily member 11 gene promoter polymorphisms modulate promoter activity and influence bone mineral density in postmenopausal women with osteoporosis. J Mol Endocrinol 2008;40:273-9.
23
Langdahl BL, Carstens M, Stenkjaer L, Eriksen EF. Polymorphisms in the osteoprotegerin gene are associated with osteoporotic fractures. J Bone Miner Res 2002;17:1245-55.
24
Vidal C, Brincat M, Anastasi AX. TNFRSF11B gene variants and bone mineral density in postmenopausal women in Malta. Maturitas 2006;53:386-95.
25
da Silva FRP, Vasconcelos ACCG, Casimiro GS, Pessoa LS, Neto APRN, Vasconcelos DFP. Quantitative assessment of the association between polymorphisms in osteoprotegerin gene and risk of low bone mineral density. Int Arch Med 2015;8:12.
26
Sun T, Chen M, Lin X, Yu R, Zhao Y, Wang J. The influence of osteoprotegerin genetic polymorphisms on bone mineral density and osteoporosis in Chinese postmenopausal women. Int Immunopharmacol 2014;22:200-3.
27
Yu F, Huang X, Miao J, Guo L, Tao D. Association between osteoprotegerin genetic variants and osteoporosis in Chinese postmenopausal women. Endocr J 2013;60:1303-7.
28
Kim JG, Kim JH, Kim JY, Ku SY, Jee BC, Suh CS, et al. Association between osteoprotegerin (OPG), receptor activator of nuclear factor-kappaB (RANK), and RANK ligand (RANKL) gene polymorphisms and circulating OPG, soluble RANKL levels, and bone mineral density in Korean postmenopausal women. Menopause 2007;14:913-8.
29
Choi JY, Shin A, Park SK, Chung HW, Cho SI, Shin CS, et al. Genetic polymorphisms of OPG, RANK, and ESR1 and bone mineral density in Korean postmenopausal women. Calcif Tissue Int 2005;77:152-9.
30
Wang J, Wang Y, Zhao Y, Li Y, Sun M, Na R, et al. Polymorphisms of genes in the OPG/RANKL/RANK pathway in the Mongols of Inner Mongolia China: relationship to other populations. Int J Clin Exp Med 2016;9:3851-9.
31
Guo L, Tang K, Quan Z, Zhao Z, Jiang D. Association between seven common OPG genetic polymorphisms and osteoporosis risk: a meta-analysis. DNA Cell Biol 2014;33:29-39.
32
Luo Y, Hu Z, Hao J, Jiang W, Shen J, Zhao J. Significant association between the the A163G and G1181C polymorphisms of the osteoprotegerin gene and risk of osteoporosis, especially in postmenopausal women: a meta-analysis. Genet Test Mol Biomarker 2014;18:211-9.
33
Shang M, Lin L, Cui H. Association of genetic polymorphisms of RANK, RANKL and OPG with bone mineral density in Chinese peri- and postmenopausal women. Clin Biochem 2013;46:1493-501.
34
Tu P, Duan P, Zhang RS, Xu DB, Wang Y, Wu HP, et al. Polymorphisms in genes in the RANK/RANKL/OPG pathway are associated with bone mineral density at different sites in postmenopausal women. Osteoporosis Int 2015;26:179-85.
35
Cvijetic S, Grazio S, Kosovic P, Uremovic M, Nemcic T, Bobic J. Osteoporosis and polymorphisms of osteoprotegerin gene in postmenopausal women – a pilot study. Reumatologia 2016;54:10-3.
36
Li S, Jiang H, Du N. Association between osteoprotegerin gene T950C polymorphisms and osteoporosis risk in the Chinese population: evidence via meta-analysis. PloS One 2017;12:e0189825.
37
Piedra M, García-Unzueta MT, Berja A, Paule B, Lavin BA, Raincho JA, et al. Single nucleotide polymorphisms of the OPG/RANKL system genes in primary hyperparathyroidism and their relationship with bone mineral density. BMC Med Genet 2011;12:168.
38
Sioka C, Fotopoulos A, Georgiou A, Xourgia X, Papadopoulos A, Kalef-Ezra JA. Age at menarche, age at menopause and duration of fertility as risk factors for osteoporosis. J Climacteric 2010;13:63-71.
39
Cristina de Sousa E Silva Araujo E, Pagotto V, Silveira EA. Bone Mineral Density in the Noninstitutionalized Elderly: Influence of Sociodemographic and Anthropometric Factors. Curr Gerontol Geriatr Res 2016;2016:4946593.
40
Prastowo NA, Ali S, Haryono IR. A population-based study on bone mineral density using Dual-Energy X-Ray Absorptiometry (DEXA) in postmenopausal women in Jakarta, Indonesia. Int J Osteoporos Metabol Disorder 2018;11:1-6.
41
Duan P, Wang ZM, Liu J, Wang LN, Yang Z, Tu P. Gene polymorphisms in RANKL/RANK/OPG pathway are associated with age at menarche and natural menopaue in Chinese women. BMC Womens Health 2015;15:32.
