THE ROLE OF POLYMORPHIC CANDIDATE GENES FOR BONE TISSUE METABOLISM (VDR BSM1 C.IVS7G>A, LCT -13910 С>Т, COL1A 2046 G>T) IN THE DEVELOPMENT OF OSTEOPOROSIS IN WOMEN OF RUSSIAN AND BURYAT NATIONALITIES IN TRANS-BAIKAL REGION

The aim of the research. To describe the frequency of occurrence of polymorphisms in bone tissue remodeling genes (vitamin D receptor gene Bsm1 c.IVS7G>A, lactase gene LCT -13910 C>T and collagen gene COL1A1 2046 G>T) in patients with osteoporosis (OP) and healthy women of Russian and Buryat nationalities in Trans-Baikal region.

Materials and methods. 121 women with OP (50 Russian and 80 Buryat nationalities aged from 50 to 80 years) and 145 healthy women of the same age were examined. The diagnosis of OP was established according to the Russian Clinical Guidelines for Osteoporosis 2021. The study of genetic polymorphism was carried out by PCR for VDR and LCT using standard sets of primers SPF "Litekh" - "SNP" (Moscow); and DNA Technology for COL1A1.

Results. Homozygous TT of LCT 13910 C>T and recessive allele A VDR - Bsm1 c.IVS7 G>A were associated with increased risk of osteoporosis in women of both nationalities. Heterozygous GА of VDR Bsm1 c.IVS7G>A, homozygous TT of LCT 13910 C>T were associated with increased risk of osteoporosis in Russian women. Homozygous АА of VDR Bsm1 c.IVS7G>A were associated with osteoporosis risk in Buryat women. Homozygous recessive TT of LCT 13910 C>T is independent predictor of osteoporotic fractures in Russian women.

Conclusion. VDR gene heterozygous GА of Bsm1 c.IVS7G>A and homozygous TT of LCT 13910 C>T were associated with osteoporosis risk in Russian women. Homozygous АА of VDR Bsm1 c.IVS7G>A is increased osteoporosis risk in women of Buryat nationality.

1. Clinical guidelines: osteoporosis. Russian Association of Endocrinologists. Public organization "Russian Association for Osteoporosis". Association of Rheumatologists of Russia. Association of Traumatologists-Orthopedists of Russia. Association of Gynecologists and Endocrinologists of Russia. All-Russian public Organization "Russian Association of Gerontologists and Geriatricians". 2021 [cited 2021 June 14]. Available by: https://cr.minzdrav.gov.ru/recomend/87_2. in Russian.

2. Kanis J. A., Norton N., Harvey N. C., Jacobson T., Johansson H., Lorentzon M., McCloskey E. V., Willers C., Borgström F. SCOPE 2021: a new scorecard for osteoporosis in Europe. Archives of osteoporosis. 2021. 16(1). 82. DOI:10.1007/s11657-020-00871-9.

3. Dobrovol'skaya O.V., Toportsova N.V., Lesnyak O.M. Economic aspects of complicated osteoporosis: the cost of treatment during the first year of fracture. Sovremennaya revmatologiya. 2016. 10(3). 29-34. in Russian. DOI: 10.14412/1996-7012-2016-3-29-34.

4. Maylyan E.A. Associations of polymorphism 283 A>G (BSMI) of the vitamin D receptor gene with osteoporosis in women depending on the duration of postmenopause. Nauchnye vedomosti Belgorodskogo gosudarstvennogo universiteta. Seriya: Meditsina. Farmatsiya. 2017. 12(261). 12-21. in Russian.

5. Fernandez C., Tennyson J., Priscilla A.S. Osteoporosis and its Association with Vitamin D Receptor, Oestrogen α Receptor, Parathyroid Receptor and Collagen Type I alpha Receptor Gene Polymorphisms with Bone Mineral Density: A Pilot Study from South Indian Postmenopausal Women of Tamil Nadu. Biochemical Genetics. 2022 Feb 23. DOI: 10.1007/s10528-022-10197-5.

6. Techapatiphandee M., Tammachote N., Tammachote R., Wongkularb.A., Yanatatsaneejit P. VDR and TNFSF11 polymorphisms are associated with osteoporosis in Thai patients. Biomedical reports. 2018. 9(4). 350-356. DOI:10.3892/br.2018.1137.

7. Yu M., Chen G.Q., Yu F. Lack of association between vitamin D receptor polymorphisms ApaI (rs7975232) and BsmI (rs1544410) and osteoporosis among the Han Chinese population: A meta-analysis. Kaohsiung J Med Sci. 2016. 32(12). 599-606. DOI: 10.1016/j.kjms.2016.10.002.

8. Rudenko E.V., Rudenko E.V., Samokhovets O.Yu., Kobets E.V., Marozik P.M.Association of polymorphic variants of the vitamin D receptor gene with bone mineral density in menopausal women. Vestnik natsional'noy akademii nauk Belorussii. 2019. 16(2). 192-201. in Russian.

9. Marozik P.M., Tamulaitiene M., Rudenka E., Alekna V., Mosse I., Rudenka A., Samokhovec V., Kobets K. Association of Vitamin D Receptor Gene Variation With Osteoporosis Risk in Belarusian and Lithuanian Postmenopausal Women. Front Endocrinol (Lausanne). 2018. 9. 305. DOI: 10.3389/fendo.2018.00305.

10. Yureneva S.V., Donnikov A.E., Bordakova E.V., Yakushevskaya O.V., Smetnik A.A., Trofimov D.Yu. Clinical and prognostic significance of molecular genetic factors in postmenopausal osteoporosis. Osteoporosis and Osteopathy. 2015. 1. 3-6. in Russian.

11. Fu L., Ma J., Yan S., Si Q. A meta-analysis of VDR polymorphisms and postmenopausal osteoporosis. Endocrine Connections. 2020. 9(9). 882-889. DOI: 10.1530/EC-20-0296.

12. Almazar A.E., Chang J.Y., Larson J.J., Atkinson E.J., Locke G.R., Talley N.J., Saito Y.A. Comparison of Lactase Variant MCM6 -13910 C>T Testing and Self-report of Dairy Sensitivity in Patients With Irritable Bowel Syndrome. Journal of Clinical Gastroenterology. 2019. 53(6). 227-231. DOI: 10.1097/MCG.0000000000001065.

13. Tereshkin K.I., Tereshkina E.I. Structural and functional state of bone tissue in young people with osteoarthritis depending on the level of plasma apelin and lactase gene polymorphism. Nauchnyy rezul'tat. Meditsina i formatsiya. 2017. 3(1).3-7. in Russian.

14. Boschmann S.E., Boldt A.B., de Souza I.R., Petzl-Erler M.L., Messias-Reason I.J. The Frequency of the LCT*-13910C>T Polymorphism Associated with Lactase Persistence Diverges among Euro-Descendant Groups from Brazil. Medical Principles and Practice. 2016. 25(1). 18-20. DOI: 10.1159/000440807.

15. Marozik P., Mosse I., Alekna V., Rudenko E., Tamulaitienė M., Ramanau H., Strazdienė V., Samokhovec V., Ameliyanovich M., Byshnev N., Gonchar A., Kundas L., Zhur K. Association Between Polymorphisms of VDR, COL1A1, and LCT genes and bone mineral density in Belarusian women with severe postmenopausal osteoporosis. Medicina (Kaunas). 2013. 49(4). 177-84. PMID: 23985982.

16. Majchrzycki M., Bartkowiak-Wieczorek J., Wolski H., Drews K., Bogacz A., Czerny B., Zagrodnik-Ułan E., Seremak-Mrozikiewicz A. Polymorphisms of collagen 1A1 (COL1A1) gene and their relation to bone mineral density in postmenopausal women. Ginekolgia Polska. 2015. 86(12). 907-14. DOI: 10.17772/gp/60550.

17. Aitkulova A., Akilzhanova A., Abilova Z., Zhumatova Z., Akilzhanova G., Zholdybayeva E. Collagen Type I alpha1 (COL1A1) Gene Polymorphism and Bone Mineral Density in Postmenopausal Kazakh Women. Central Asian Journal of Global Health. 2014. 12(3). 144. DOI: 10.5195/cajgh.2014.144.

18. Wu J., Yu M., Zhou Y. Association of collagen type I alpha 1 +1245G/T polymorphism and osteoporosis risk in post-menopausal women: a meta-analysis. International Journal of Rheumatic Diseases. 2017. 20(7). 903-910. DOI: 10.1111/1756-185X.13052.

19. Rojano-Mejía D., Coral-Vázquez RM., Espinosa LC., López-Medina G., Aguirre-García M.C., Coronel A., Canto P. JAG1 and COL1A1 polymorphisms and haplotypes in relation to bone mineral density variations in postmenopausal Mexican-Mestizo Women. Age (Dordr). 2013. 35(2). 471-8. DOI: 10.1007/s11357-011-9363-9.

20. Dytfeld J., Marcinkowska M., Drwęska-Matelska N., Michalak M., Horst-Sikorska W., Słomski R. Association analysis of the COL1A1 polymorphism with bone mineral density and prevalent fractures in Polish postmenopausal women with osteoporosis. Arch Med Sci. 2016. 12(2). 288-94. DOI: 10.5114/aoms.2016.59253.