ESTIMATION OF THE FREQUENCY OF GENETIC VARIANTS ASSOCIATED WITH VITAMIN D LEVELS AND OSTEOPOROSIS IN THE POPULATION OF UKRAINE

Authors

DOI:

https://doi.org/10.21856/j-PEP.2022.2.08

Keywords:

vitamin D, osteoporosis, genome, single nucleotide polymorphisms

Abstract

Circulating vitamin D levels and the risk of osteoporosis have significant inheritance. Single nucleotide polymorphisms (SNPs) in the GC, DHCR7/NADSYN1, CYP2R1, CYP24A1, and SEC23A genes have shown significant association with these conditions in previous genome-wide association studies (GWAS). Objective: to study the frequency of alleles associated with circulating levels of vitamin D and osteoporosis in the cohort of Ukrainians, as well as to compare the frequencies of these variants with individuals of Western and Northern European origin.

Materials and Methods. This paper presents the results of the study of the frequencies of genomic variants associated with vitamin D levels and osteoporosis in a cohort of 97 Ukrainians based on genome data obtained by whole genome sequencing (WGS), as well as comparing their frequencies with the combined European population (CEU) of the "1000 genomes" project (persons of Western and Northern European ancestry). Files with the primary publicly available genomic data of Ukrainians were annotated using ANNOVAR and SNPEff software using the reference database of the human genome version hg38. Comparison of allele frequencies between populations was performed using Fisher's exact test using the number of alleles in the two studied populations and the construction of conjugated 2x2 tables.

Results. It was found that of the 22 single nucleotide polymorphisms included in the analysis, 10, namely rs2282679; rs4855; rs10033936; rs3755967; rs17467825; rs12639968; rs1155563; rs17216707; rs10745742; rs180119, significantly differ in the Ukrainian cohort comparatively to CEU. Using correlation analysis, we also found that the genotypes of SNPs rs3755967, rs17467825, rs2282679 and rs4855 in Ukrainians are completely correlated with each other (r = 1), which means that they are in a state of complete linkage in Ukrainians of the given cohorts.

Conclusion. Such findings may be the evidence of evolutionary and adaptation processes in the regulation of vitamin D levels and bone mineral density in the population of Ukraine and requires further studies of phenotype-genotype relationship.

References

Hunter D, De Lange M, Snieder H, et al. J Bone Miner Res 2001;16(2): 371-378. https://doi.org/10.1359/jbmr.2001.16.2.371

Karohl C, Su S, Kumari M, et al. Am J Clin Nutr 2010; 92(6): 1393-1398. https://doi.org/10.3945/ajcn.2010.30176

Wang TJ, Zhang F, Richards JB, et al. Lancet 2010; 376(9736): 180-188. https://doi.org/10.1016/S0140-6736(10)60588-0

Ahn J, Yu K, Stolzenberg-Solomon R, et al. Hum Mol Genet 2010;19(13): 2739-2745. https://doi.org/10.1093/hmg/ddq155

Jiang X, O’Reilly PF, Aschard H, et al. Nat Commun 2018;9(1): 1-12. https://doi.org/10.1038/s41467-017-02662-2

Boyadjiev SA, Fromme JC, Ben J, et al. Nat Genet 2006; 38(10): 1192-1197. https://doi.org/10.1038/ng18

Manousaki D, Dudding T, Haworth S, et al. Am J Hum Genet 2017;101(2): 227-238. https://doi.org/10.1016/j.ajhg.2017.06.014.

Oleksyk TK, Wolfsberger WW, Weber AM, et al. Gigascience 2021;10(1): giaa159. https://doi.org/10.1093/gigascience/giaa159

Auton A, Brooks LD, Durbin RM, et al. Nature 2015; 526: 68-74. https://doi.org/10.1038/nature15393

Lasky-Su J, Lange N, Brehm JM, et al. Hum Genet 2012;131(9): 1495-1505. https://doi.org/10.1007/s00439-012-1185-z

Ganz AB, Park H, Malysheva O V, Caudill MA. FASEB J 2018;32(4): 2012-2020. https://doi.org/10.1096/fj.201700992R

Jia F, Sun R-F, Li Q-H, et al. Genet Test Mol Biomarkers 2013;17(1): 30-34. https://doi.org/10.1089/gtmb.2012. 0267

Jakubowska-Pietkiewicz E, Młynarski W, Klich I, et al. Mol Biol Rep 2012;39(5): 6243-6250. https://doi.org/10.1007/s11033-012-1444-z

Esterle L, Jehan F, Sabatier J-P, Garabedian M. J Bone Miner Res 2009;24(8): 1389-1397. https://doi.org/10.1359/jbmr.090301

Falcón-Ramirez E, Casas-Avila L, Cerda-Flores RM, et al. Mol Biol Rep 2013;40(3): 2705-2710. https://doi.org/10.1007/s11033-012-2357-6

Kitjaroentham A, Hananantachai H, Phonrat B, et al. J Negat Results Biomed 2016;15(1): 1-10. https://doi.org/10.1186/s12952-016-0059-7

van Meurs JBJ, Trikalinos TA, Ralston SH, et al. JAMA 2008;299(11): 1277-1290. https://doi.org/10.1001/jama.299.11.1277

Tranah GJ, Taylor BC, Lui L-Y, et al. Calcif Tissue Int 2008;83(3): 155-166. https://doi.org/10.1007/s00223-008-9165-y

van Dijk FS, Zillikens MC, Micha D, et al. N Engl J Med 2013;369(16): 1529-1536. https://doi.org/10.1056/NEJMoa1308223

St-Arnaud R, Jones G. Vitamin D, Fourth Edition 2018: 81-95. https://doi.org/10.1016/C2015-0-05921-4

Myung JK, Jeong JB, Han D, et al. Pathol Oncol Res 2011;17(2): 415-420. https://doi.org/10.1007/s12253-010-9322-2

Purdue BW, Tilakaratne N, Sexton PM. Recept Channels 2002;8(3-4): 243-255.

Tural S, Kara N, Alayli G, Tomak L. Gene 2013;515(1): 167-172. https://doi.org/10.1016/j.gene.2012.10.041

Dehghan M, Pourahmad-Jaktaji R, Farzaneh Z. Acta Inform Medica 2016;24(4): 239. https://doi.org/10.5455/aim.2016.24.239-243

Mitra P, Guha M, Ghosh S, et al. Gene 2017;622: 23-28. https://doi.org/10.1016/j.gene.2017.04.033

Downloads

Published

2022-06-09

How to Cite

Shchubelka, K., Wolfsberger, W., Oleksyk, O., & Oleksyk, T. (2022). ESTIMATION OF THE FREQUENCY OF GENETIC VARIANTS ASSOCIATED WITH VITAMIN D LEVELS AND OSTEOPOROSIS IN THE POPULATION OF UKRAINE. Problems of Endocrine Pathology, 79(2), 53-59. https://doi.org/10.21856/j-PEP.2022.2.08

Issue

Section

CLINICAL ENDOCRINOLOGY