POLYMORPHISM OF METHYLENETETRAHYDROFOLATE REDUCTASE (A1298C) AS A RISK FACTOR FOR OSTEOPOROSIS IN POST-MENOPAUSAL INDONESIAN WOMEN

Abstract

 

 Objective: The study aimed to assess the association between the A1298C polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene and risk to osteoporosis in post-menopausal Indonesian women.

Methods: After ethical approval, calcaneus bone mineral density (BMD) (T-scoring) was assessed from 194 consenting post-menopausal Indonesian women by dual-energy X-ray absorptiometry, and DNA of the participants was isolated from peripheral blood samples. To determine the status of A1298C polymorphism of MTHFR, isolated DNA was polymerase chain reaction (PCR) amplified in 35 cycles, to result in PCR product sizes of 302 bp (1298A) and 275 bp (1298C). For fragment detection, the PCR product was subjected to electrophoresis on agarose gel. The results were statistically assessed for genotype and allotype comparison according to the T-score grouping by Chi-square analysis, assuming statistical significance at p<0.05.

Results: The results show no significant association between the T-score (BMD) grouping and genotype (or allotype) of the tested polymorphism of MTHFR. The observed genotype distribution of the tested MTHFR polymorphism (A1298C) differs clearly from those previously reported, with AC as the dominant genotype in the Indonesian sample population of the present work.

Conclusion: The MTHFR (A1298C) polymorphism is relatively infrequent in the Indonesian female population, and no significant association was observed between this polymorphism, bone mineral density, and osteoporotic status.

Keywords: Menopause, Osteoporosis, Methylenetetrahydrofolate reductase, Polymorphism, Bone mineral density.

Author Biography

Elza Ibrahim Auerkari, University of Indonesia
Department of Oral Biology, Faculty of Dentistry

References

1. Raisz LG. Pathogenesis of osteoporosis: Concepts, conflicts, and prospects. J Clin Invest 2005;115(12):3318-25.
2. Duncan EL, Brown MA. Genetic studies in osteoporosis-the end of the beginning. Arthritis Res Ther 2008;10(5):214.
3. Rachner TD, Khosla S, Hofbauer LC. Osteoporosis: Now and the future. Lancet 2011;377(9773):1276-87.
4. Nelson HD. Menopause. Lancet 2008;371(9614):760-70.
5. Ralston SH, de Crombrugghe B. Genetic regulation of bone mass and susceptibility to osteoporosis. Genes Dev 2006;20(18):2492-506.
6. Riancho JA, Valero C, Zarrabeitia MT. MTHFR polymorphism and bone mineral density: Meta-analysis of published studies. Calcif Tissue Int 2006;79(5):289-93.
7. Li D, Wu J. Association of the MTHFR C677T polymorphism and bone mineral density in postmenopausal women: A meta-analysis. J Biomed Res 2010;24(6):417-23.
8. Tsai MY, Loria CM, Cao J, Kim Y, Siscovick DS, Schreiner PJ, et al. Polygenic association with total homocysteine in the post-folic acid fortification era: The CARDIA study. Mol Genet Metab 2009;98(1-2):181-6.
9. Angeline T, Jeyaraj N, Granito S, Tsongalis GJ. Prevalence of MTHFR gene polymorphisms (C677T and A1298C) among tamilians. Exp Mol Pathol 2004;77(2):85-8.
10. Auerkari EI, Suryandari DA, Umami SS, Kusdhany LS, Siregar TW, Rahardjo TB, et al. Gene promoter polymorphism of RUNX2 and risk of osteoporosis in postmenopausal Indonesian women. SAGE Open Med 2014;2:2050312114531571.
11. Auerkari E, Suhartono A, Djamal N, Verisqa F, Suryandari D, Kusdhany L, et al. CRP and IL-1B gene polymorphisms and CRP in blood in periodontal disease. Open Dent J 2013;7:88-93.
12. Aléssio AC, Höehr NF, Siqueira LH, Bydlowski SP, Annichino-Bizzacchi JM. Polymorphism C776G in the transcobalamin II gene and homocysteine, folate and vitamin B12 concentrations. Association with MTHFR C677T and A1298C and MTRR A66G polymorphisms in healthy children. Thromb Res 2007;119(5):571-7.
13. Zhang C, Xie B, Fang Y, Cheng W, Du Y, Wang D, et al. Influence of maternal MTHFR A1298C polymorphism on the risk in offspring of schizophrenia. Brain Res 2010;1320:130-4.
14. Hiraoka M, Kato K, Saito Y, Yasuda K, Kagawa Y. Gene-nutrient and gene-gene interactions of controlled folate intake by Japanese women. Biochem Biophys Res Commun 2004;316(4):1210-6.
15. Yang B, Fan S, Zhi X, Xia R, Wang Y, Zheng Q, et al. Geographical and ethnic distribution of MTHFR gene polymorphisms and their association with diseases among Chinese population. Clin Genet 2017. DOI: 10.1111/ege.12929.
16. Karmadonova NA, Shilova AN, Kozyreva VS, Subbotovskaya AI, Klevanets JE, Karpenko AA. Association of folate metabolism and pulmonary embolism: A case-control study of West-Siberian population. Thromb Res 2015;135:788-95.
17. Pols HA, Yazdanpanah Y, van Meurs JB. Homocysteine, the vitamin B complex family and bone. Int Congr Ser 2007;1297:151-7.
18. Bhaskar LV, Murthy J, Venkatesh Babu G. Polymorphisms in genes involved in folate metabolism and orofacial clefts. Arch Oral Biol 2011;56(8):723-37.
19. Basu P, Sunny A, Maier C. Estrogenic and antiestrogenic activities of commercial dietary supplements containing herbal ingredients and is flavones. Int J Pharm Pharm Sci 2016;8:307-12.
20. Kumar PR, Joseph AK, Gokul G, Alex MP, Naveena G. Clinical outcome of calcium, vitamin D3 and physiotherapy in osteoporotic population in the Nilgiris district. Int J Pharm Pharm Sci 2016;8:157-60.
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Auerkari, E. I., L. Kusdhany, S. S. Umami, T. B. W. Rahardjo, and C. Talbot. “POLYMORPHISM OF METHYLENETETRAHYDROFOLATE REDUCTASE (A1298C) AS A RISK FACTOR FOR OSTEOPOROSIS IN POST-MENOPAUSAL INDONESIAN WOMEN”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 10, no. 10, Sept. 2017, pp. 172-5, doi:10.22159/ajpcr.2017.v10i10.20272.
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