Association of vitamin D status and genetic variants with type 2 diabetes in a Costa Rican population
DOI:
https://doi.org/10.51481/amc.v68i1.1517Keywords:
25-hydroxyvitamin D, SNPs, obesity, genetic association studies, Diabetes Mellitus, Type 2Abstract
Aim: To assess the association between plasma 25-hydroxyvitamin D levels, gene polymorphisms involved in vitamin D metabolism, and the risk of type 2 diabetes in a Costa Rican population. Methods: 578 adults were enrolled in a case-control study from an urban Costa Rican population. Blood samples were collected to measure circulating vitamin D levels, glucose, hemoglobin A1c, lipid profile, and for the genotyping of 14 vitamin D related SNPs. The associations between plasma 25-hydroxyvitamin D levels, clinical and biochemical variables, gene polymorphisms, and type 2 diabetes were tested. Results: Classical risks factors as body mass index (OR: 1.13, p <0.001), and arterial hypertension (OR: 3.31, p <0.001) were associated with type 2 diabetes. In addition, type 2 diabetes was associated with 25-hydroxyvitamin D levels (OR: 0.97, p = 0.023). Polymorphisms in the GC gene (rs4588, rs7041, rs3755967, and rs22522679) were associated with plasma levels of vitamin D (all-p values <0.036). None of the SNPs assessed were associated with type 2 diabetes. Conclusion: Our findings suggest that GC gene polymorphisms contribute to interindividual variability in vitamin D status. Although these variants were not directly associated with type 2 diabetes in the present study, their potential role in vitamin D–related metabolic pathways warrant further investigation.
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References
1. Christakos S, Dhawan P, Verstuyf A, Verlinden L, Carmeliet G. Vitamin D: metabolism, molecular mechanism of action, and pleiotropic effects vitamin D analogs. Physiol Rev. 2016;96:365–408. DOI: 10.1152/physrev.00014.2015
2. Pilz S, Verheyen N, Grübler MR, Tomaschitz A, März W. Vitamin D and cardiovascular disease prevention. Nat Rev Cardiol. 2016;13:404–17. DOI:10.1038/nrcardio.2016.73
3. Mitri J, Muraru MD, Pittas AG. Vitamin D and type 2 diabetes: A systematic review. Eur J Clin Nutr. 2011;65:1005–15. DOI: 10.1038/ejcn.2011.118
4. Ahn J, Yu K, Stolzenberg-Solomon R, Claire Simon K, McCullough ML, Gallicchio L, et al. Genome-wide association study of circulating vitamin D levels. Hum Mol Genet. 2010;19:2739–45. DOI: 10.1093/hmg/ddq155
5. Jorde R, Schirmer H, Wilsgaard T, Joakimsen RM, Mathiesen EB, Njølstad I, et al. Polymorphisms related to the serum 25-Hydroxyvitamin D level and risk of Myocardial infarction, diabetes, cancer and mortality. The Tromsø study. PLoS One. 2012;7:1–10. DOI: 10.1371/journal.pone.0037295
6. Engelman CD, Fingerlin TE, Langefeld CD, Hicks PJ, Rich SS, Wagenknecht LE, et al. Genetic and environmental determinants of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels in Hispanic and African Americans. J Clin Endocrinol Metab. 2008;93:3381–8. DOI: 10.1210/jc.2007-2702
7. Scragg R, Sowers M, Bell C. Serum 25-hydroxyvitamin D, Diabetes and Ethnicity in the Third National Health and Nutrition Examination Survey. Diabetes Care. 2004;27:2813–8. DOI: 10.2337/diacare.27.12.2813
8. Kayaniyil S, Retnakaran R, Harris S, Vieth R, Knight J, Gerstein H, et al. Association of Vitamin D with Insulin Resistance and beta-Cell Dysfunction in Subjects at Risk for Type 2 Diabetes. Diabetes Care. 2010;33:6–8. DOI: 10.2337/dc09-2321
9. Gobbo LC Del, Song Y, Dannenbaum DA, Dewailly E, Egeland GM. Serum 25-Hydroxyvitamin D is not Associated with Insulin Resistance or Beta Cell Function in Canadian Cree. J Nutr. 2011;141:290–5. DOI: 10.3945/jn.110.129619
10. Marques-vidal P, Vollenweider P, Guessous I, Henry H, Boulat O. Serum Vitamin D Concentrations Are Not Associated with Insulin Resistance in Swiss. J Nutr. 2015;145:2117–22. DOI: 10.3945/jn.115.211763
11. Wu C, Qiu S, Zhu X, Li L. Vitamin D supplementation and glycemic control in type 2 diabetes patients: A systematic review and meta-analysis. Metabolism. 2017;73:67–76. DOI: 10.1016/j.metabol.2017.05.006
12. Kawahara T. Eldecalcitol, a Vitamin D Analog, for Diabetes Prevention in Impaired Glucose Tolerance (DPVD Study). Diabetes. 2018 May 1;67:120-LB. DOI: 10.2337/db18-120-LB
13. Pittas AG, Dawson-Hughes B, Sheehan P, Ware JH, Knowler WC, Aroda VR, et al. Vitamin D Supplementation and Prevention of Type 2 Diabetes. N Engl J Med. 2019;381:520–30. DOI: 10.1056/NEJMoa1900906
14. Zeitz U, Weber K, Soegiarto DW, Wolf E, Balling R, Reinhold G, et al. Impaired insulin secretory capacity in mice lacking a functional vitamin D receptor. FASEB J. 2003;17:509–11. DOI: 10.1096/fj.02-0424fje
15. Wolden-Kirk H, Overbergh L, Gysemans C, Brusgaard K, Naamane N, Van Lommel L, et al. Unraveling the effects of 1,25(OH)2D3 on global gene expression in pancreatic islets. J Steroid Biochem Mol Biol. 2013;136:68–79. DOI: 10.1016/j.jsbmb.2012.10.017
16. Albala C, Vio F. Obesity and Diabetes in Latin America: The Impact of Socioeconomic Status on Programs and Outcomes. In: Romero T, Nazal CN, Lanas F, editors. Global Challenges in Cardiovascular Prevention in Populations with Low Socioeconomic Status. Cham: Springer. 2025. p. 51–61. DOI: 10.1007/978-3-031-79051-5_3
17. Caja Costarricense del Seguro Social. Informe de Resultados de la Evaluación de la Prestación de Servicios de Salud 2020 y Tendencias del 2021. San José (CR): EDNASSS; 2021. ISBN: 9789968916912
18. Campos H, Willett WC, Peterson RM, Siles X, Bailey SM, Wilson PWF, et al. Nutrient Intake Comparisons Between Framingham and Rural and Urban Puriscal, Costa Rica. Arterioscler Thromb. 1991;11:1089–99. DOI: 10.1161/01.atv.11.4.1089
19. Campos H, Mata L, Siles X, Vives M, Ordovas JM, Schaefer EJ, et al. Prevalence of Cardiovascular Risk Factors in Rural and Urban Costa Rica. Circulation. 1992;85:648–59. DOI: 10.1161/01.cir.85.2.648
20. Laclé-Murray A, Valero-Juan L. Incidencia de diabetes tipo 2 en un área urbano marginal de Costa Rica. Acta Med Costarric. 2008;50:29–34. DOI: 10.51481/amc.v50i1.349
21. Gómez Salas G, Ramírez Sanabria A, Sheik Oreamuno A, Chinnock A, Nogueira Previdelli A, Hermes Sales C, et al. Prevalencia de ingesta inadecuada de micronutrientes en la población urbana de Costa Rica. Arch Latinoam Nutr. 2019;69:221–32. DOI: 10.37527/2019.69.4.003
22. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2011;34. DOI: 10.2337/dc11-S062
23. WHO. Obesity: preventing and managing the global epidemic. World Health Organ Tech Rep Ser. 2000;894:1–253. PMID: 11234459.
24. Holick MF, Binkley NC, Bischoff-ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, Treatment , and Prevention of Vitamin D Deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2011;96:1911–30. DOI: 10.1210/jc.2011-0385
25. Engelman CD, Meyers KJ, Ziegler JT, Taylor KD, Palmer ND, Haffner SM, et al. Genome-wide association study of vitamin D concentrations in Hispanic Americans: The IRAS Family Study. J Steroid Biochm Mol Biol. 2010;122:186–92. DOI: 10.1016/j.jsbmb.2010.06.013
26. Wang T, Zhang F, Richards B, Kestenbaum B, van Meurs J, Berry D, et al. Common genetic determinants of vitamin D insufficiency: genome-wide association study. Lancet. 2010;376:180–8. DOI: 10.1016/S0140-6736(10)60588-0
27. Afzal S, Brøndum-Jacobsen P, Bojesen SE, Nordestgaard BG. Vitamin D concentration, obesity, and risk of diabetes: A mendelian randomisation study. Lancet Diabetes Endocrinol. 2014;2:298–306. DOI: 10.1016/S2213-8587(13)70200-6
28. Ye Z, Sharp SJ, Burgess S, Scott RA, Imamura F, Langenberg C, et al. Association between circulating 25-hydroxyvitamin D and incident type 2 diabetes: A mendelian randomisation study. Lancet Diabetes Endocrinol. 2015;3:35–42. DOI: 10.1016/S2213-8587(14)70184-6.
29. Price AL, Patterson NJ, Plenge RM, Weinblatt ME, Shadick NA, Reich D. Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet. 2006;38:904–9. DOI: 10.1038/ng1847
30. Chang CC, Chow CC, Tellier LC, Vattikuti S, Purcell SM, Lee JJ. Second-generation PLINK: rising to the challenge of larger and richer datasets. Gigascience. 2015;4:7. DOI: 10.1186/s13742-015-0047-8
31. Roden M, Shulman GI. The integrative biology of type 2 diabetes. Nature. 2019;576:51–60. DOI: 10.1038/s41586-019-1797-8
32. Pearson ER. Type 2 diabetes: a multifaceted disease. Diabetologia. 2019;62:1107–12. DOI: 10.1007/s00125-019-4909-y
33. Castro-Bonilla N, Holst-Schumacher I, Arroyo-Portilla C, Valverde-Barrantes JM, Vargas-Soto M, Barrantes-Santamaría M. Prevalence of low 25(OH)-Vitamin D levels in Costa Rican university students. Acta Med Costarric. 2023;65:1-10. DOI:10.51481/amc.v65i2.1292.
34. Chun RF, Peercy BE, Orwoll ES, Nielson CM, Adams JS, Hewison M. Vitamin D and DBP: The free hormone hypothesis revisited. J Steroid Biochem Mol Biol. 2014;144PA:132–7. DOI: 10.1016/j.jsbmb.2013.09.012
35. Speeckaert M, Huang G, Delanghe JR, Taes YEC. Biological and clinical aspects of the vitamin D binding protein (Gc-globulin) and its polymorphism. Clinica Chimica Acta. 2006;372:33–42. DOI: 10.1016/j.cca.2006.03.011
36. Cleve H, Constans J. The Mutants of the Vitamin?D?Binding Protein: More than 120 Variants of the GC/DBP System. Vox Sang. 1988;54:215–25. DOI: 10.1111/j.1423-0410.1988.tb03908.x.
37. Rivera-Paredez B, Macías N, Martínez-Aguilar MM, Hidalgo-Bravo A, Flores M, Quezada-Sánchez AD, et al. Association between vitamin D deficiency and single nucleotide polymorphisms in the vitamin D receptor and GC genes and analysis of their distribution in Mexican postmenopausal women. Nutrients. 2018;10:1175. DOI: 10.3390/nu10091175.
38. Contreras-Bolívar V, García-Fontana B, García-Fontana C, Muñoz-Torres M. Mechanisms involved in the relationship between vitamin D and insulin resistance: impact on clinical practice. Nutrients. 2021 Oct 1;13:3491. DOI: 10.3390/nu13103491.
39. American Diabetes Asocciation. 2. Classification and diagnosis of diabetes: Standards of medical care in diabetes - 2019. Diabetes Care. 2019;42:S13–28. DOI: 10.2337/dc19-S002
40. Echouffo-Tcheugui JB, Niiranen TJ, McCabe EL, Jain M, Vasan RS, Larson MG, et al. Lifetime prevalence and prognosis of prediabetes without progression to diabetes. Diabetes Care. 2018;41:117–8. DOI: 10.2337/dc18-0524.
41. Brannick B, Dagogo-Jack S. Prediabetes and Cardiovascular Disease: Pathophysiology and Interventions for Prevention and Risk Reduction. Endocrinol Metab Clin North Am. 2018;47:33–50. DOI: 10.1016/j.ecl.2017.10.001
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