Variants in the Gene May Influence 25(OH)D Levels in Type 1 Diabetes Mellitus in a Brazilian Population

Overview

Journal Nutrients

Date 2022 Mar 10

PMID 35267984

Authors

Rafaella S Ferraz

Caio S Silva

Giovanna C Cavalcante

Natercia N M de Queiroz

Karem M Felicio

Joao S Felicio

Andrea Ribeiro-Dos-Santos

Affiliations

Soon will be listed here.

Abstract

Vitamin D has been considered a strong contributing factor to type 1 diabetes mellitus (T1DM). Many studies have investigated polymorphisms in the gene in association with T1DM in different populations, but there are still conflicting findings. This study aimed to evaluate the association of four variants in the gene (rs7975232, rs1544410, rs731236, and rs2228570) with T1DM risk and vitamin D levels within a population from North Region, Brazil, as well as the influence of genomic ancestry on T1DM. A total of 65 T1DM patients and 83 non-T1DM patients were enrolled in this study. gene polymorphisms were assessed using Sanger sequencing analysis. Genomic ancestry was analyzed using a set of 61 ancestry-informative markers. T1DM patients showed higher European genomic contribution and lower Native American genomic contribution when compared to non-T1DM patients. T1DM patients with AA genotype in rs1544410 or CC genotype in rs731236 had significantly lower 25(OH)D levels compared to the other two genotypes ( = 0.013 and = 0.02, respectively), while T1DM with TT genotype in rs2228570 had higher 25(OH)D levels compared to CC + TC in the same polymorphism ( = 0.011). Our findings suggest that the association between 25(OH)D and T1DM may be modified by variants, possibly influencing the development of this autoimmune disease.

Citing Articles

The vitamin D receptor TaqI TT genotype is associated with type 1 diabetes in the Black South African population.

Bhola S, Cave E, Prigge K, Bhana S, Crowther N, Padoa C J Nutr Sci. 2024; 13:e73.

PMID: 39703896 PMC: 11658941. DOI: 10.1017/jns.2024.77.

The impact of genetic variants related to vitamin D and autoimmunity: A systematic review.

Trefilio L, Bottino L, de Carvalho Cardoso R, Montes G, Fontes-Dantas F Heliyon. 2024; 10(7):e27700.

PMID: 38689997 PMC: 11059421. DOI: 10.1016/j.heliyon.2024.e27700.

Vitamin D-associated genetic variants in the Brazilian population: Investigating potential instruments for Mendelian randomization.

De Souza Silverio C, Bonilla C Biomedica. 2024; 44(1):45-53.

PMID: 38648345 PMC: 11349065. DOI: 10.7705/biomedica.6972.

Genetic Variations in Susceptibility to Traumatic Muscle Injuries and Muscle Pain among Brazilian High-Performance Athletes.

Marques I, Tavares V, Neto B, Lopes L, Goes R, Matheus Guimaraes J Int J Mol Sci. 2024; 25(6).

PMID: 38542272 PMC: 10969868. DOI: 10.3390/ijms25063300.

Interaction between Fokl polymorphism and vitamin D deficiency in the symptoms of mental disorders in adults: a population-based study.

Sabiao T, de Menezes-Junior L, Batista A, de Moura S, Meireles A, de Menezes M Sci Rep. 2024; 14(1):6925.

PMID: 38519539 PMC: 10960038. DOI: 10.1038/s41598-024-57558-1.

References

Neves J, Queiroz D, Araujo E, Lacerda L, do Nascimento R, Carvalho A . Variants rs1544410 and rs2228570 of the vitamin D receptor gene and glycemic levels in adolescents from Northeast Brazil. Nutr Hosp. 2019; 37(1):21-27. DOI: 10.20960/nh.02587. View

Reis A, Hauache O, Velho G . Vitamin D endocrine system and the genetic susceptibility to diabetes, obesity and vascular disease. A review of evidence. Diabetes Metab. 2005; 31(4 Pt 1):318-25. DOI: 10.1016/s1262-3636(07)70200-8. View

Ribeiro de Andrade Ramos B, DElia M, Amador M, Santos N, Emanuel Batista Santos S, Castelli E . Neither self-reported ethnicity nor declared family origin are reliable indicators of genomic ancestry. Genetica. 2016; 144(3):259-65. DOI: 10.1007/s10709-016-9894-1. View

Santos N, Ribeiro-Rodrigues E, Ribeiro-Dos-Santos A, Pereira R, Gusmao L, Amorim A . Assessing individual interethnic admixture and population substructure using a 48-insertion-deletion (INSEL) ancestry-informative marker (AIM) panel. Hum Mutat. 2009; 31(2):184-90. DOI: 10.1002/humu.21159. View

Mathieu C, Badenhoop K . Vitamin D and type 1 diabetes mellitus: state of the art. Trends Endocrinol Metab. 2005; 16(6):261-6. DOI: 10.1016/j.tem.2005.06.004. View

Norman A, Frankel J, Heldt A, GRODSKY G . Vitamin D deficiency inhibits pancreatic secretion of insulin. Science. 1980; 209(4458):823-5. DOI: 10.1126/science.6250216. View

Raab J, Giannopoulou E, Schneider S, Warncke K, Krasmann M, Winkler C . Prevalence of vitamin D deficiency in pre-type 1 diabetes and its association with disease progression. Diabetologia. 2014; 57(5):902-8. DOI: 10.1007/s00125-014-3181-4. View

Gysemans C, Cardozo A, Callewaert H, Giulietti A, Hulshagen L, Bouillon R . 1,25-Dihydroxyvitamin D3 modulates expression of chemokines and cytokines in pancreatic islets: implications for prevention of diabetes in nonobese diabetic mice. Endocrinology. 2005; 146(4):1956-64. DOI: 10.1210/en.2004-1322. View

Rasoul M, Haider M, Al-Mahdi M, Al-Kandari H, Dhaunsi G . Relationship of four vitamin D receptor gene polymorphisms with type 1 diabetes mellitus susceptibility in Kuwaiti children. BMC Pediatr. 2019; 19(1):71. PMC: 6404350. DOI: 10.1186/s12887-019-1448-0. View

10.

Nejentsev S, Cooper J, Godfrey L, Howson J, Rance H, Nutland S . Analysis of the vitamin D receptor gene sequence variants in type 1 diabetes. Diabetes. 2004; 53(10):2709-12. DOI: 10.2337/diabetes.53.10.2709. View

11.

Chakhtoura M, Azar S . The role of vitamin d deficiency in the incidence, progression, and complications of type 1 diabetes mellitus. Int J Endocrinol. 2013; 2013:148673. PMC: 3610375. DOI: 10.1155/2013/148673. View

12.

Abd-Allah S, Pasha H, Hagrass H, Alghobashy A . Vitamin D status and vitamin D receptor gene polymorphisms and susceptibility to type 1 diabetes in Egyptian children. Gene. 2013; 536(2):430-4. DOI: 10.1016/j.gene.2013.12.032. View

13.

Uitterlinden A, Fang Y, van Meurs J, Pols H, van Leeuwen J . Genetics and biology of vitamin D receptor polymorphisms. Gene. 2004; 338(2):143-56. DOI: 10.1016/j.gene.2004.05.014. View

14.

Andrade R, Amador M, Cavalcante G, Leitao L, Fernandes M, Modesto A . Estimating Asian Contribution to the Brazilian Population: A New Application of a Validated Set of 61 Ancestry Informative Markers. G3 (Bethesda). 2018; 8(11):3577-3582. PMC: 6222592. DOI: 10.1534/g3.118.200650. View

15.

Atkinson M, Eisenbarth G, Michels A . Type 1 diabetes. Lancet. 2013; 383(9911):69-82. PMC: 4380133. DOI: 10.1016/S0140-6736(13)60591-7. View

16.

Moran-Auth Y, Penna-Martinez M, Badenhoop K . VDR FokI polymorphism is associated with a reduced T-helper cell population under vitamin D stimulation in type 1 diabetes patients. J Steroid Biochem Mol Biol. 2015; 148:184-6. DOI: 10.1016/j.jsbmb.2015.01.003. View

17.

Lemos M, Fagulha A, Coutinho E, Gomes L, Bastos M, Barros L . Lack of association of vitamin D receptor gene polymorphisms with susceptibility to type 1 diabetes mellitus in the Portuguese population. Hum Immunol. 2008; 69(2):134-8. DOI: 10.1016/j.humimm.2008.01.008. View

18.

Norris J, Lee H, Frederiksen B, Erlund I, Uusitalo U, Yang J . Plasma 25-Hydroxyvitamin D Concentration and Risk of Islet Autoimmunity. Diabetes. 2017; 67(1):146-154. PMC: 5741144. DOI: 10.2337/db17-0802. View

19.

Cheon C, Nam H, Lee K, Kim S, Song J, Kim C . Vitamin D receptor gene polymorphisms and type 1 diabetes mellitus in a Korean population. Pediatr Int. 2015; 57(5):870-4. DOI: 10.1111/ped.12634. View

20.

Holick M, Binkley N, Bischoff-Ferrari H, Gordon C, Hanley D, Heaney R . Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011; 96(7):1911-30. DOI: 10.1210/jc.2011-0385. View