Vitamin D-associated genetic variants in the Brazilian population: Investigating potential instruments for Mendelian randomization
Abstract
Introduction. Vitamin D is required for bone and mineral metabolism and participates in the regulation of the immune response. It is also linked to several chronic diseases and conditions, usually in populations of European descent. Brazil presents a high prevalence of vitamin D deficiency and insufficiency despite the widespread availability of sunlight in the country. Thus, it is important to investigate the role of vitamin D as a risk factor for disease and to establish causal relationships between vitamin D levels and health-related outcomes in the Brazilian population.
Objective. To examine genetic variants identified as determinants of serum vitamin D in genome-wide association studies of European populations and check whether the same associations are present in Brazil. If so, these single nucleotide polymorphisms (SNPs) could be developed locally as proxies to use in genetically informed causal inference methods, such as Mendelian randomization.
Materials and methods. We extracted SNPs associated with vitamin D from the genomewide association studies catalog. We did a literature search to select papers ascertaining these variants and vitamin D concentrations in Brazil.
Results. GC was the gene with the strongest association with vitamin D levels, in agreement with existing findings in European populations. However, VDR was the
most investigated gene, regardless of its non-existing association with vitamin D in the genomewide association studies.
Conclusions. More research is needed to validate sound proxies for vitamin D levels in Brazil, for example, prioritizing GC rather than VDR.
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References
Holick MF. Optimal vitamin D status for the prevention and treatment of osteoporosis. Drugs Aging. 2007;24:1017-29. https://doi.org/10.2165/00002512-200724120-00005
Charoenngam N, Holick MF. Immunologic effects of vitamin D on human health and disease. Nutrients. 2020;12:2097. https://doi.org/10.3390/nu12072097
Pilz S, Grübler M, Gaksch M, Schwetz V, Trummer C. Vitamin D and mortality. Anticancer Res. 2016;36:1379-88.
Bandera-Merchan B, Morcillo S, Martin-Nuñez G, Tinahones FJ, Macías-González M. The role of vitamin D and VDR in carcinogenesis: Through epidemiology and basic sciences. J Steroid Biochem Mol Biol. 2017;167:203-18. https://doi.org/10.1016/j.jsbmb.2016.11.020
Vieth R, Holick MF. The IOM—Endocrine Society controversy on recommended vitamin D targets. In: Vitamin D: Volume One: Biochemistry, Physiology and Diagnostics. 4th edition. Cambridge, MA: Academic Press; 2018. p. 1091-107. https://doi.org/10.1016/B978-0-12-809965-0.00059-8
Smith GD, Ebrahim S. ‘Mendelian randomization’: can genetic epidemiology contribute to understanding environmental determinants of disease? Int J Epidemiol. 2003;32:1-22. https://doi.org/10.1093/ije/dyg070
Bennett DA, Du H. An overview of methods and exemplars of the use of Mendelian randomisation in nutritional research. Nutrients. 2022;14:3408. https://doi.org/10.3390/nu14163408
Global Core Biodata Resource. GWAS Catalog. Accessed: October 1, 2021. Available at: https://www.ebi.ac.uk/gwas/
National Library of Medicine. PubMed. Accessed: January 10, 2022. Available at : https://pubmed.ncbi.nlm.nih.gov/
Pan-American Health Organization. LILACS, scientific health information from Latin America and the Caribbean countries. Accessed: January 10, 2022. Available at: https://lilacs.bvsalud.org/
Elsevier B. V. Scopus. Accessed: January 10, 2022. Available at: https://www.scopus.com/
Red SciELO. Scielo, Scientific Electronic Library Online. Accessed: January 10, 2022. Available at: https://scielo.org/
Instituto Brasileiro de Informação em Ciência e Tecnologia. Biblioteca Digital Brasileira de Teses e Dissertacoes. Accessed: January 10, 2022. Available at: http://bdtd.ibict.br/vufind/
Cobayashi F, Lourenço BH, Cardoso MA. 25-hydroxyvitamin D3 levels, BsmI polymorphism and insulin resistance in Brazilian Amazonian children. Int J Mol Sci. 2015;16:12531-46. https://doi.org/10.3390/ijms160612531
Santos BR, Mascarenhas LPG, Satler F, Boguszewski MCS, Spritzer PM. Vitamin D deficiency in girls from South Brazil: A cross-sectional study on prevalence and association with vitamin D receptor gene variants. BMC Pediatr. 2012;12:606. https://doi.org/10.1186/1471-2431-12-62
Ferraz RS, Silva CS, Cavalcante GC, de Queiroz NNM, Felício KM, Felício JS, et al. Variants in the VDR gene may influence 25(OH)D levels in type 1 diabetes mellitus in a Brazilian population. Nutrients. 2022;14:1010. https://doi.org/10.3390/nu14051010
Galvão AA, de Araújo Sena F, de Andrade Belitardo EMM, de Santana MBR, Costa GN de O, Cruz ÁA, et al. Genetic polymorphisms in vitamin D pathway influence 25(OH)D levels and are associated with atopy and asthma. Allergy Asthma Clin Immunol. 2020;16:62. https://doi.org/10.1186/s13223-020-00460-y
Bezerra FF, Normando P, Fonseca ACP, Zembrzuski V, Campos-Junior M, Cabello-Acero PH, et al. Genetic, sociodemographic and lifestyle factors associated with serum 25-hydroxyvitamin D. Cad Saúde Publica. 2022;38:e00287820. https://doi.org/10.1590/0102-311X00287820
Brait BJ, da Silva Lima SP, Aguiar FL, Fernandes-Ferreira R, OliveiraBrancati CIF, Ferraz JAML, et al. Genetic polymorphisms related to the vitamin D pathway in patients with cirrhosis with or without hepatocellular carcinoma (HCC). Ecancermedicalscience. 2022;16:1383. https://doi.org/10.3332/ecancer.2022.1383
Vidigal VM, Silva TD, de Oliveira J, Pimenta CAM, Felipe AV, Forones NM. Genetic polymorphisms of vitamin D receptor (VDR), CYP27B1 and CYP24A1 genes and the risk of colorectal cancer. Int J Biol Markers. 2017;32:e224-30. https://doi.org/10.5301/jbm.5000248
de Paula Corrêa M, Pires LCM. Doses of erythemal ultraviolet radiation observed in Brazil. Int J Dermatol. 2013;52:966-73. https://doi.org/10.1111/j.1365-4632.2012.05834.x
Pereira-Santos M, dos Santos JYG, Carvalho GQ, Santos DB, Oliveira AM. Epidemiology of vitamin D insufficiency and deficiency in a population in a sunny country: Geospatial metaanalysis in Brazil. Crit Rev Food Sci Nutr. 2019;59:2102-9. https://doi.org/10.1080/10408398.2018.1437711
Mendes MM, Hart KH, Botelho PB, Lanham-New SA. Vitamin D status in the tropics: Is sunlight exposure the main determinant? Nutr Bull. 2018;43:428-34. https://doi.org/10.1111/nbu.12349
Maeda SS, Borba VZC, Camargo MBR, Silva DMW, Borges JLC, Bandeira F, et al. Recomendações da Sociedade Brasileira de Endocrinologia e Metabologia (SBEM) para o diagnóstico e tratamento da hipovitaminose D. Arq Bras Endocrinol Metabol. 2014;58:411-33. https://doi.org/10.1590/0004-2730000003388
Ahn J, Yu K, Stolzenberg-Solomon R, Simon KC, McCullough ML, Gallicchio L, et al. Genome-wide association study of circulating vitamin D levels. Hum Mol Genet. 2010;19:2739-45. https://doi.org/10.1093/hmg/ddq155
Wang TJ, Zhang F, Richards JB, Kestenbaum B, van Meurs JB, Berry D, et al. Common genetic determinants of vitamin D insufficiency: A genome-wide association study. Lancet. 2010;376:180-8. https://doi.org/10.1016/S0140-6736(10)60588-0
Hong J, Hatchell KE, Bradfield JP, Bjonnes A, Chesi A, Lai CQ, et al. Transethnic evaluation identifies low-frequency loci associated with 25-hydroxyvitamin D concentrations. J Clin Endocrinol Metab. 2018;103:1380-92. https://doi.org/10.1210/jc.2017-01802
Kim YA, Yoon JW, Lee Y, Choi HJ, Yun JW, Bae E, et al. Unveiling genetic variants underlying vitamin D deficiency in multiple Korean cohorts by a genome-wide association study. Endocrinol Metab. 2021;36:1189-200. https://doi.org/10.3803/EnM.2021.1241
Parlato LA, Welch R, Ong IM, Long J, Cai Q, Steinwandel MD, et al. Genome-wide association study (GWAS) of circulating vitamin D outcomes among individuals of African ancestry. Am J Clin Nutr. 2023;117:308-16. https://doi.org/10.1016/j.ajcnut.2022.12.001
Manousaki D, Mitchell R, Dudding T, Haworth S, Harroud A, Forgetta V, et al. Genomewide association study for vitamin D levels reveals 69 independent loci. Am J Hum Genet. 2020;106:327-37. https://doi.org/10.1016/j.ajhg.2020.01.017
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