Vitamin D status in connection with VDR and GC genes polymorphism in coal mining workers
AbstractVitamin D is a unique compound that can enter the human body not only with food, but also be synthesized in the skin under the influence of ultraviolet radiation. Individual differences in the need for this vitamin may be associated with the carriage of polymorphic variants of genes that implement its biological effects, which include VDR BsmI C>T (rs1544410), VDR TaqI A>G (rs731236) and GC rs2282679 T>G. At risk for vitamin D deficiency are workers in the coal mining industry, whose working conditions combine limited insolation and a pronounced deficiency of vitamins in the diet.
The purpose of the study was to assess vitamin D plasma level in coal mining workers depending on the carriage of polymorphic variants of the VDR BsmI C>T (rs1544410), VDR TaqI A>G (rs731236) and GC rs2282679 T>G genes and professional working conditions.
Material and methods. The study included 154 coal mining workers. The main group consisted of 100 workers associated with the underground nature of work, the comparison group – 54 ground workers of the enterprise. In all individuals, the level of 25-hydroxyvitamin D in blood plasma was determined by enzyme-linked immunosorbent assay and genotyping was performed for three polymorphic loci: VDR rs1544410, rs731236, GC rs2282679 by real-time PCR.
Results. A statistically significant decrease in the concentration of plasma vitamin D in the underground workers was revealed, compared with the level of this vitamin in ground workers of the enterprise (p=0.037). Underground workers – carriers of the CT genotype of the VDR rs1544410 gene, AG of the VDR rs731236 gene and TT of the GC rs2282679 gene had a lower 25(OH)D level in blood plasma compared to owners of similar genotype variants in the comparison group (p<0.05). Among ground workers, carriers of the TT genotype of the GC rs2282679 gene had a significantly higher vitamin D plasma level compared to carriers of the TG and GG genotypes (p=0.02). An association of the GC gene with vitamin D level in blood plasma was revealed according to a dominant model of inheritance (OR=0.47, 95% CI 0.23–0.97; p=0.037, for owners of the TT genotype, compared with carriers of the TG+GG genotypes).
Conclusion. The development of personalized diets based on individual genetic status may be of great importance for the prevention of diseases associated with vitamin D deficiency in individuals at risk.
Keywords:vitamin D; blood plasma; genetic polymorphism; coal mining workers; underground working conditions; personalized diet
Funding. This research was supported by the «Priority 2030» program № 075-15-2023-244 dated 02/14/2023.
Conflict of interest. The authors declare no conflict of interest.
Contribution. Concept of the study – Minina V.I., Milentyeva I.S.; collection of the data – Minina V.I., Soboleva O.A., Torgunakova A.V.; DNA extraction, genotyping – Titov R.A., Yakovleva A.A.: statistical analysis of the data, writing the article – Soboleva O.A., Torgunakova A.V., Minina V.I., Asyakina L.K.; scientific consulting, editing – Prosekov A.Yu.; approval of the final version of the article, responsibility for the integrity of all parts and content of the article – all authors.
Acknowledgment. The authors express gratitude to the staff of the «Energetik» Medical Research Center for their assistance in collecting biological material and conducting an analysis to determine vitamin D level in blood plasma of the study participants.
For citation: Soboleva O.A., Minina V.I., Torgunakova A.V., Titov R.A., Yakovleva A.A., Milentyeva I.S., Asyakina L.K., Prosekov A.Yu. Vitamin D status in connection with VDR and GC genes polymorphism in coal mining workers. Voprosy pitaniia [Problems of Nutrition]. 2024; 93 (4): 74–83. DOI: https://doi.org/10.33029/0042-8833-2024-93-4-74-83 (in Russian)
References
1. Fadavi P., Nafisi N., Hariri R., Novin K., Sanei M., Razzaghi Z., et al. Serum ferritin, vitamin D and pathological factors in breast cancer patients. Med J Islam Repub Iran. 2021; 35: 162. DOI: https://doi.org/10.47176/mjiri.35.162
2. Rosso C., Fera N., Murugan N.J., Voutsadakis I.A. Vitamin D levels in newly diagnosed breast cancer patients according to tumor sub-types. J Diet Suppl. 2023; 20 (6): 926–38. DOI: https://doi.org/10.1080/19390211.2022.2144582
3. De la Guía-Galipienso F., Martínez-Ferran M., Vallecillo N., Lavie C.J., Sanchis-Gomar F., Pareja-Galeano H. Vitamin D and cardiovascular health. Clin Nutr. 2021; 40 (5): 2946–57. DOI: https://doi.org/10.1016/j.clnu.2020.12.025
4. Cakal S., Çakal B., Karaca O. Association of vitamin D deficiency with arterial stiffness in newly diagnosed hypertension. Blood Press Monit. 2021; 26 (2): 113–7. DOI: https://doi.org/10.1097/MBP.0000000000000497
5. Denos M., Mai X.M., Asvold B.O., Sorgjerd E.P., Chen Y., Sun Y.Q. Vitamin D status and risk of type 2 diabetes in the Norwegian HUNT cohort study: does family history or genetic predisposition modify the association? BMJ Open Diabetes Res Care. 2021; 9 (1): e001948. DOI: https://doi.org/10.1136/bmjdrc-2020-001948
6. Geng T., Lu Q., Wan Z., Guo J., Liu L., Pan A, Liu G. Association of serum 25-hydroxyvitamin D concentrations with risk of dementia among individuals with type 2 diabetes: a cohort study in the UK Biobank. PLoS Med. 2022; 19 (1): e1003906. DOI: https://doi.org/10.1371/journal.pmed.1003906
7. Hanel A., Neme A., Malinen M., Hämäläinen E., Malmberg H.R., Etheve S., et al. Common and personal target genes of the micronutrient vitamin D in primary immune cells from human peripheral blood. Sci Rep. 2020; 10 (1): 21051. DOI: https://doi.org/10.1038/s41598-020-78288-0
8. Gaml-Sørensen A., Brix N., Hærvig K.K., Lindh C., Tottenborg S.S., Hougaard K.S., et al. Maternal vitamin D levels and male reproductive health: a population-based follow-up study. Eur J Epidemiol. 2023; 38 (5): 469–84. DOI: https://doi.org/10.1007/s10654-023-00987-5
9. Holick M.F. Vitamin D deficiency. N Engl J Med. 2007; 357 (3): 266–81. DOI: https://doi.org/10.1056/NEJMra070553
10. Malyarchuk B.A. Polymorphism of GC gene, encoding vitamin D binding protein, in aboriginal population of Siberia. Ekologicheskaya genetika [Ecological Genetics]. 2020; 18 (2): 243–50. DOI: https://doi.org/10.17816/ecogen18634 (in Russian)
11. Shibanova N.Yu. To the question about the organization of subterranean feeding of working on coal mines of Kuzbass. Meditsina v Kuzbasse [Medicine in Kuzbass]. 2009; 8 (3): 43–7. (in Russian)
12. Baturin A.K., Sorokina E.Yu., Vrzhesinskaya O.A., Beketova N.A., Sokol’nikov A.A., Kobel’kova I.V., et al. The study of the association between rs2228570 polymorphism of VDR gene and vitamin D blood serum concentration in the inhabitants of the Russian Arctic. Voprosy pitaniia [Problems of Nutrition]. 2017; 86 (4): 77–84. DOI: https://doi.org/10.24411/0042-8833-2017-00062 (in Russian)
13. Uitterlinden A.G., Fang Y., Van Meurs J.B.J., Pols H.A.P., Van Leeuwen J.P.T.M. Genetics and biology of vitamin D receptor polymorphisms. Gene. 2004; 338 (2): 143–56. DOI: https://doi.org/10.1016/j.gene.2004.05.014
14. Imani D., Razi B., Motallebnezhad M., Rezaei R. Association between vitamin D receptor (VDR) polymorphisms and the risk of multiple sclerosis (MS): an updated meta-analysis. BMC Neurol. 2019; 19 (1): 339. DOI: https://doi.org/10.1186/s12883-019-1577-y
15. Asghari G., Yuzbashian E., Najd-Hassan-Bonab L., Mirmian P., Daneshpour M.S., Azizi F. Association of rs2282679 polymorphism in vitamin D binding protein gene (GC) with the risk of vitamin D deficiency in an Iranian population: season-specific vitamin D status. BMC Endocr Disord. 2023; 23 (1): 217. DOI: https://doi.org/10.1186/s12902-023-01463-7
16. Kondratyeva E.I., Zakharova I.N., Ilenkova N.A., Klimov L.Y., Petrova N.V., Zodbinova A.E., et al. Vitamin D status in russian children and adolescents: contribution of genetic and exogenous factors. Front Pediatr. 2020; 19 (8): 583206. DOI: https://doi.org/10.3389/fped.2020.583206
17. Pludowski P., Holick M.F., Pilz S., Wagner C.L., Hollis B.W., Grant W.B., et al. Vitamin D effects on musculoskeletal health, immunity, autoimmunity, cardiovascular disease, cancer, fertility, pregnancy, dementia and mortality-a review of recent evidence. Autoimmun Rev. 2013; 12 (10): 976–89. DOI: https://doi.org/10.1016/j.autrev.2013.02.004
18. Khodabakhshi A., Mahmoudabadi M., Vahid F. The role of serum 25 (OH) vitamin D level in the correlation between lipid profile, body mass index (BMI), and blood pressure. Clin Nutr ESPEN. 2022; 48 (4): 421–6. DOI: https://doi.org/10.1016/j.clnesp.2022.01.007
19. Pérez-Bravo F., Duarte L., Arredondo-Olguín M., Iñiguez G., Castillo-Valenzuela O. Vitamin D status and obesity in children from Chile. Eur J Clin Nutr. 2022; 76 (6): 899–901. DOI: https://doi.org/10.1038/s41430-021-01043-9
20. Alathari B.E., Aji A.S., Ariyasra U., Sari S.R., Tasrif N., Yani F.F., et al. Interaction between vitamin D-related genetic risk score and carbohydrate intake on body fat composition: a study in Southeast Asian Minangkabau women. Nutrients. 2021; 13 (2): 326. DOI: https://doi.org/10.3390/nu13020326
21. Radulović Ž., Zupan Z.P., Tomazini A., Varda N.M. Vitamin D in pediatric patients with obesity and arterial hypertension. Sci Rep. 2021; 11 (1): 19591. DOI: https://doi.org/10.1038/s41598-021-98993-8
22. Brot C., Jorgensen N.R., Sorensen O.H. The influence of smoking on vitamin D status and calcium metabolism. Eur J Clin Nutr. 1999; 53 (12): 920–6. DOI: https://doi.org/10.1038/sj.ejcn.1600870
23. Shan X., Zhao X., Li S., Hu Y., Yang L. Association of vitamin D gene polymorphisms and serum 25-hydroxyvitamin D in Chinese women of childbearing age. Wei Sheng Yan Jiu. 2022; 51 (6): 961–8. DOI: https://doi.org/10.19813/j.cnki.weishengyanjiu.2022.06.017
24. Foucan L., Vélayoudom-Céphise F.L., Larifla L., Armand C., Deloumeaux J., Fagour C., et al. Polymorphisms in GC and NADSYN1 Genes are associated with vitamin D status and metabolic profile in non-diabetic adults. BMC Endocr Disord. 2013; 29 (13): 36. DOI: https://doi.org/10.1186/1472-6823-13-36
25. Feng M., Zhang D., Liu Y., Zhao T., Huang H., Zhang L., et al. GC gene polymorphisms found with type 2 diabetes and low vitamin D status among rural Chinese in Henan province. Asia Pac J Clin Nutr. 2022; 31 (2): 331–9. DOI: https://doi.org/10.6133/apjcn.202206_31(2).0019
26. Nissen J., Rasmussen L.B., Ravn-Haren G., Andersen E.W., Hansen B., Andersen R., et al. Common variants in CYP2R1 and GC genes predict vitamin D concentrations in healthy Danish children and adults. PLoS One. 2014; 9 (2): 89907. DOI: https://doi.org/10.1371/journal.pone.0089907
27. Sentsova T.B., Denisova S.N., Ni A., Kachalova O.V. Vitamin D provision in children with allergic diseases with polymorphic variants of the VDR gene. Tikhookeanskiy meditsinskiy zhurnal [Pacific Medical Journal]. 2019; (4): 29–31. DOI: https://doi.org/10.34215/1609-1175-2019-4-29-31 (in Russian)
28. Yerezhepov D., Gabdulkayum A., Akhmetova A., Kozhamkulov U.A., Rakhimova S.E., Kairov U.Y., et al. Vitamin D status, VDR, and TLR polymorphisms and pulmonary tuberculosis epidemiology in Kazakhstan. Nutrients. 2024; 16 (4): 558. DOI: https://doi.org/10.3390/nu16040558
29. Karonova T., Grineva E., Belyaeva O., Bystrova A., Jude E.B., Andreeva A. et al. Relationship between vitamin D status and vitamin D receptor gene polymorphisms with markers of metabolic syndrome among adults. Front Endocrinol. 2018; 16 (9): 448. DOI: https://doi.org/10.3389/fendo.2018.00448
30. Mao R., Zhou G., Jing D., Liu H., Shen M., Li J. Vitamin D status, Vitamin D receptor polymorphisms, and the risk of incident rosacea: insights from mendelian randomization and cohort study in the UK biobank. Nutrients. 2023; 15 (17): 3803. DOI: https://doi.org/10.3390/nu15173803
31. Bushuyeva T.V., Borovik T.E., Zvonkova N.G., Lukoyanova O.L., Semenova N.N., Skvortsova V.A., et al. The role of nutrition in vitamin D provision. Prakticheskaya meditsina [Practical Medicine]. 2017; (5): 14–8. (in Russian)
32. Grigor’eva N.M., Kuleshova M.V. The dangers of trans fats in food: the problem of public awareness. Vestnik Chelyabinskogo gosudarstvennogo universiteta. Obrazovaniye i zdravookhraneniye [Bulletin of the Chelyabinsk State University. Education and Healthcare]. 2020; 4 (12): 54–8. DOI: https://doi.org/10.24411/2409-4102-2020-10407 (in Russian)