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BMC Endocrine Disorders
Published in: BMC Endocrine Disorders 1/2020

01-12-2020 | Diabetes | Research article

Vitamin D receptor gene polymorphisms and the risk of the type 1 diabetes: a meta-regression and updated meta-analysis

Authors: Na Zhai, Ramtin Bidares, Masoud Hassanzadeh Makoui, Saeed Aslani, Payam Mohammadi, Bahman Razi, Danyal Imani, Mohammad Yazdchi, Haleh Mikaeili

Published in: BMC Endocrine Disorders | Issue 1/2020

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Abstract

Background

The association between the polymorphisms in the vitamin D receptor (VDR) gene and the risk of type 1 diabetes mellitus (T1DM) has been evaluated in several studies. However, the findings were inconclusive. Thus, we conducted a meta-analysis to comprehensively evaluate the effect of VDR gene polymorphisms on the risk of T1DM.

Methods

All relevant studies reporting the association between VDR gene polymorphisms and susceptibility to T1DM published up to May 2020 were identified by comprehensive systematic database search in ISI Web of Science, Scopus, and PubMed/MEDLINE. Strength of association were assessed by calculating of pooled odds ratios (ORs) and 95% confidence intervals (CIs). The methodological quality of each study was assessed according to the Newcastle–Ottawa Scale. To find the potential sources of heterogeneity, meta-regression and subgroup analysis were also performed.

Results

A total of 39 case–control studies were included in this meta-analysis. The results of overall population rejected any significant association between VDR gene polymorphisms and T1DM risk. However, the pooled results of subgroup analysis revealed significant negative and positive associations between FokI and BsmI polymorphisms and T1DM in Africans and Americans, respectively.

Conclusions

This meta-analysis suggested a significant association between VDR gene polymorphism and T1DM susceptibility in ethnic-specific analysis.
Literature
1.
Gupta G, et al. A clinical update on metformin and lung cancer in diabetic patients. Panminerva Med. 2018;60(2):70–5.PubMedCrossRef
2.
3.
Miettinen ME, et al. Genetic determinants of serum 25-hydroxyvitamin D concentration during pregnancy and type 1 diabetes in the child. PLoS One. 2017;12(10):e0184942.PubMedPubMedCentralCrossRef
4.
Diaz-Valencia PA, Bougnères P, Valleron A-J. Global epidemiology of type 1 diabetes in young adults and adults: a systematic review. BMC Public Health. 2015;15(1):255.PubMedPubMedCentralCrossRef
5.
6.
Vaidya A, Williams JS. The relationship between vitamin D and the renin-angiotensin system in the pathophysiology of hypertension, kidney disease, and diabetes. Metabolism. 2012;61(4):450–8.PubMedCrossRef
7.
Riek AE, et al. Vitamin D suppression of endoplasmic reticulum stress promotes an antiatherogenic monocyte/macrophage phenotype in type 2 diabetic patients. J Biol Chem. 2012;287(46):38482–94.PubMedPubMedCentralCrossRef
8.
Makoui MH, Imani D, Motallebnezhad M, Azimi M, Razi B. Vitamin D receptor gene polymorphism and susceptibility to asthma: Meta-analysis based on 17 case-control studies. Ann Allergy Asthma Immunol. 2020;124(1):57–69.PubMedCrossRef
9.
Bagheri-Hosseinabadi Z, et al. Vitamin D receptor (VDR) gene polymorphism and risk of rheumatoid arthritis (RA): systematic review and meta-analysis. Clin Rheumatol. 2020.
10.
Bhalla AK, et al. 1, 25-Dihydroxyvitamin D3 inhibits antigen-induced T cell activation. J Immunol. 1984;133(4):1748–54.PubMed
11.
Lemire JM. Immunomodulatory actions of 1, 25-dihydroxyvitamin D3. J Steroid Biochem Mol Biol. 1995;53(1–6):599–602.PubMedCrossRef
12.
Riachy R, et al. 1, 25-Dihydroxyvitamin D 3 protects human pancreatic islets against cytokine-induced apoptosis via down-regulation of the Fas receptor. Apoptosis. 2006;11(2):151–9.PubMedCrossRef
13.
Trembleau S, et al. The role of IL-12 in the induction of organ-specific autoimmune diseases. Immunol Today. 1995;16(8):383–6.PubMedCrossRef
14.
Uitterlinden AG, et al. Genetics and biology of vitamin D receptor polymorphisms. Gene. 2004;338(2):143–56.PubMedCrossRef
15.
Panierakis C, et al. Vitamin D receptor gene polymorphisms and susceptibility to type 1 diabetes in Crete, Greece. Clin Immunol. 2009;133(2):276–81.PubMedCrossRef
16.
Wang Q, et al. Quantitative assessment of the associations between four polymorphisms (FokI, ApaI, BsmI, TaqI) of vitamin D receptor gene and risk of diabetes mellitus. Mol Biol Rep. 2012;39(10):9405–14.PubMedCrossRef
17.
Ferrari S, et al. Vitamin D receptor gene start codon polymorphisms (FokI) and bone mineral density: interaction with age, dietary calcium, and 3′-end region polymorphisms. J Bone Miner Res. 1998;13(6):925–30.PubMedCrossRef
18.
Imani D, et al. Association between vitamin D receptor (VDR) polymorphisms and the risk of multiple sclerosis (MS): an updated meta-analysis. BMC Neurol. 2019;19(1):339.PubMedPubMedCentralCrossRef
19.
Valdivielso JM, Fernandez E. Vitamin D receptor polymorphisms and diseases. Clin Chim Acta. 2006;371(1–2):1–12.PubMedCrossRef
20.
Tizaoui K, et al. Contribution of VDR polymorphisms to type 1 diabetes susceptibility: systematic review of case–control studies and meta-analysis. J Steroid Biochem Mol Biol. 2014;143:240–9.PubMedCrossRef
21.
Guo S-W, et al. Meta-analysis of vitamin D receptor polymorphisms and type 1 diabetes: a HuGE review of genetic association studies. Am J Epidemiol. 2006;164(8):711–24.PubMedCrossRef
22.
Zhang J, et al. Polymorphisms in the vitamin D receptor gene and type 1 diabetes mellitus risk: an update by meta-analysis. Mol Cell Endocrinol. 2012;355(1):135–42.PubMedCrossRef
23.
Sahin OA, et al. Association of vitamin D receptor polymorphisms and type 1 diabetes susceptibility in children: a meta-analysis. Endocr Connections. 2017;6(3):159–71.CrossRef
24.
Qin W-H, et al. A meta-analysis of association of vitamin D receptor BsmI gene polymorphism with the risk of type 1 diabetes mellitus. J Recept Signal Transduct. 2014;34(5):372–7.CrossRef
25.
Wang G, et al. Associations between two polymorphisms (FokI and BsmI) of vitamin D receptor gene and type 1 diabetes mellitus in Asian population: a meta-analysis. PLoS One. 2014;9(3):e89325.PubMedPubMedCentralCrossRef
26.
Moher D, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151(4):264–9.CrossRefPubMed
27.
Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25(9):603–5.PubMedCrossRef
28.
Huedo-Medina TB, et al. Assessing heterogeneity in meta-analysis: Q statistic or I2 index? Psychol Methods. 2006;11(2):193.PubMedCrossRef
29.
DerSimonian R, Laird N. Meta-analysis in clinical trials control. Clin Trials. 1986;7:177–88. Find this article online.CrossRef
30.
Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22(4):719–48.PubMed
31.
32.
Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50:1088–101.PubMedCrossRef
33.
Ban Y, et al. Vitamin D receptor initiation codon polymorphism influences genetic susceptibility to type 1 diabetes mellitus in the Japanese population. BMC Med Genet. 2001;2(1):7.PubMedPubMedCentralCrossRef
34.
Fassbender W, et al. VDR gene polymorphisms are overrepresented in German patients with type 1 diabetes compared to healthy controls without effect on biochemical parameters of bone metabolism. Horm Metab Res. 2002;34(06):330–7.PubMedCrossRef
35.
Gyorffy B, et al. Gender-specific association of vitamin D receptor polymorphism combinations with type 1 diabetes mellitus. Eur J Endocrinol. 2002;147(6):803–8.PubMedCrossRef
36.
Turpeinen H, et al. Vitamin D receptor polymorphisms: no association with type 1 diabetes in the Finnish population. Eur J Endocrinol. 2003;149(6):591–6.PubMedCrossRef
37.
Martí G, Audí L, Esteban C, Oyarzábal M, Chueca M, Gussinyé M, Yeste D, Fernández-Cancio M, Andaluz P, Carrascosa A. Asociación de los polimorfismos del gen del receptor de la vitamina D con la diabetes mellitus tipo 1 en dos poblaciones españolas. Med Clín. 2004;123(8):286–90.
38.
Pedro JS, et al. Heterogeneity of vitamin D receptor gene association with celiac disease and type 1 diabetes mellitus. Autoimmunity. 2005;38(6):439–44.CrossRef
39.
Zemunik T, et al. FokI polymorphism, vitamin D receptor, and interleukin-1 receptor haplotypes are associated with type 1 diabetes in the Dalmatian population. J Mol Diagn. 2005;7(5):600–4.PubMedPubMedCentralCrossRef
40.
Capoluongo E, et al. Slight association between type 1 diabetes and “ff” VDR FokI genotype in patients from the Italian Lazio region. Lack of association with diabetes complications. Clin Biochem. 2006;39(9):888–92.PubMedCrossRef
41.
Lemos MC, et al. 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.PubMedCrossRef
42.
43.
Mory DB, et al. Prevalence of vitamin D receptor gene polymorphisms FokI and BsmI in Brazilian individuals with type 1 diabetes and their relation to β-cell autoimmunity and to remaining β-cell function. Hum Immunol. 2009;70(6):447–51.PubMedCrossRef
44.
Yavuz DG, et al. Vitamin D receptor gene BsmI, FokI, ApaI, TaqI polymorphisms and bone mineral density in a group of Turkish type 1 diabetic patients. Acta Diabetol. 2011;48(4):329–36.CrossRef
45.
Yokota I, et al. Association between vitamin D receptor genotype and age of onset in juvenile Japanese patients with type 1 diabetes. Diabetes Care. 2002;25(7):1244.PubMedCrossRef
46.
Bonakdaran, S., et al., Vitamin D receptor gene polymorphisms in type 1 diabetes mellitus: a new pattern from Khorasan province, Islamic Republic of Iran. 2012.
47.
Sahin SB, et al. Fas, Fas ligand, and vitamin D receptor FokI gene polymorphisms in patients with type 1 diabetes mellitus in the Aegean region of Turkey. Genet Test Mol Biomark. 2012;16(10):1179–83.CrossRef
48.
Mohammadnejad Z, et al. Association between vitamin D receptor gene polymorphisms and type 1 diabetes mellitus in Iranian population. Mol Biol Rep. 2012;39(2):831–7.PubMedCrossRef
49.
Vedralová M, et al. Polymorphisms in the vitamin D receptor gene and parathyroid hormone gene in the development and progression of diabetes mellitus and its chronic complications, diabetic nephropathy and non-diabetic renal disease. Kidney Blood Press Res. 2012;36(1):1–9.PubMedCrossRef
50.
Greer RM, et al. Serum vitamin D levels are lower in Australian children and adolescents with type 1 diabetes than in children without diabetes. Pediatr Diabetes. 2013;14(1):31–41.PubMedCrossRef
51.
Hamed EO, et al. Vitamin D level and Fok-I vitamin D receptor gene polymorphism in Egyptian patients with type-1 diabetes. Egypt J Immunol. 2013;20(2):1–10.PubMed
52.
Abd-Allah SH, et al. Vitamin D status and vitamin D receptor gene polymorphisms and susceptibility to type 1 diabetes in Egyptian children. Gene. 2014;536(2):430–4.PubMedCrossRef
53.
El-Kafoury AA, et al. The association of polymorphic sites in some genes with type 1 diabetes mellitus in a sample of Egyptian children. Egypt J Med Hum Genet. 2014;15(3):265–72.CrossRef
54.
Nasreen M, et al. Serum vitamin D levels and gene polymorphisms (Fok1 and Apa1) in children with type I diabetes and healthy controls. JPMA. 2016;66:1215.
55.
56.
57.
Rasoul MA, et al. Relationship of four vitamin D receptor gene polymorphisms with type 1 diabetes mellitus susceptibility in Kuwaiti children. BMC Pediatr. 2019;19(1):71.PubMedPubMedCentralCrossRef
58.
Chang TJ, et al. Vitamin D receptor gene polymorphisms influence susceptibility to type 1 diabetes mellitus in the Taiwanese population. Clin Endocrinol. 2000;52(5):575–80.CrossRef
59.
Škrabić V, et al. Vitamin D receptor polymorphism and susceptibility to type 1 diabetes in the Dalmatian population. Diabetes Res Clin Pract. 2003;59(1):31–5.PubMedCrossRef
60.
Bianco M, et al. Vitamin D receptor polymorphisms: are they really associated with type 1 diabetes? Eur J Endocrinol. 2004;151(5):641–2.PubMedCrossRef
61.
García D, et al. VDR polymorphisms influence the immune response in type 1 diabetic children from Santiago, Chile. Diabetes Res Clin Pract. 2007;77(1):134–40.PubMedCrossRef
62.
Cheon CK, et al. Vitamin D receptor gene polymorphisms and type 1 diabetes mellitus in a Korean population. Pediatr Int. 2015;57(5):870–4.PubMedCrossRef
63.
Khalid KE. Vitamin D receptor gene polymorphisms in Sudanese children with type 1 diabetes. AIMS Genet. 2016;3(3):167–76.CrossRef
64.
Iyer A, et al. Relationship between vitamin D receptor gene polymorphisms and type 1 diabetes mellitus in Saudi patients. Int J Pharmacol. 2017;13(8):1092–7.CrossRef
65.
Ahmed AE-A, et al. Vitamin D receptor rs7975232, rs731236 and rs1544410 single nucleotide polymorphisms, and 25-hydroxyvitamin D levels in Egyptian children with type 1 diabetes mellitus: effect of vitamin D co-therapy. Diabetes Metab Syndr Obes. 2019;12:703.PubMedPubMedCentralCrossRef
66.
Hauache O, et al. Vitamin D receptor gene polymorphism: correlation with bone mineral density in a Brazilian population with insulin-dependent diabetes mellitus. Osteoporos Int. 1998;8(3):204–10.PubMedCrossRef
67.
Motohashi Y, et al. Vitamin D receptor gene polymorphism affects onset pattern of type 1 diabetes. J Clin Endocrinol Metab. 2003;88(7):3137–40.PubMedCrossRef
68.
Shimada A, et al. Evidence for association between vitamin D receptor BsmI polymorphism and type 1 diabetes in Japanese. J Autoimmun. 2008;30(4):207–11.PubMedCrossRef
69.
Tawfeek M, Habib F, Saultan EM. Vitamin D receptor BsmI gene polymorphisms and gestational diabetes mellitus: a Saudi study. Br J Med Med Res. 2011;1(4):459–68.CrossRef
70.
Al-Moubarak SH. Gender-specific association of vitamin D receptor polymorphism Bsm-I with type 1 diabetes mellitus. Int J Pharm Sci Rev Res. 2013;21(2):254–7.
71.
Martí G, et al. Asociación de los polimorfismos del gen del receptor de la vitamina D con la diabetes mellitus tipo 1 en dos poblaciones españolas. Med Clin. 2004;123(8):286–90.CrossRef
72.
Ponsonby A-L, et al. Variation in associations between allelic variants of the vitamin D receptor gene and onset of type 1 diabetes mellitus by ambient winter ultraviolet radiation levels: a meta-regression analysis. Am J Epidemiol. 2008;168(4):358–65.PubMedCrossRef
73.
Kimlin MG, Olds WJ, Moore MR. Location and vitamin D synthesis: is the hypothesis validated by geophysical data? J Photochem Photobiol B Biol. 2007;86(3):234–9.CrossRef
Metadata
Title
Vitamin D receptor gene polymorphisms and the risk of the type 1 diabetes: a meta-regression and updated meta-analysis
Authors
Na Zhai
Ramtin Bidares
Masoud Hassanzadeh Makoui
Saeed Aslani
Payam Mohammadi
Bahman Razi
Danyal Imani
Mohammad Yazdchi
Haleh Mikaeili
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Endocrine Disorders / Issue 1/2020
Electronic ISSN: 1472-6823
DOI
https://doi.org/10.1186/s12902-020-00575-8

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