Skip to main content
SpringerLink
Log in

Association between vitamin D receptor gene polymorphisms and type 1 diabetes mellitus in Iranian population

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Type 1 diabetes mellitus (T1DM) is one of the T-cell mediated autoimmune diseases and vitamin D suppresses activation of T-cell and has immunomodulatory effects. In this study the association between four vitamin D receptor (VDR) gene polymorphisms, at positions FokI, BsmI, ApaI and TaqI, and susceptibility to T1DM was investigated. We assessed 87 Iranian patients with T1DM and one hundred healthy controls with no history of diabetes or other autoimmune diseases. Our results demonstrated that genotypes frequency of the TaqI VDR polymorphism differed significantly between T1DM patients and controls, TT genotype and T allele was more frequent in healthy controls compared with TIDM patients (P = 0.003; OR = 0.51, 95% CI = 0.31–0.84). Therefore, allele t is the risk-allele for developing TIDM in this study. No significant association was observed between others VDR SNPs and disease susceptibility. In conclusion, our case-control study indicated that the VDR TaqI polymorphism is associated with TIDM in Iranian population.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Todd JA, Fukui Y, Kitagawa T, Sasazuki T (1990) The A3 allele of the HLA-DQA1 locus is associated with susceptibility to type 1 diabetes in Japanese. Proc Natl Acad Sci USA 87(3):1094–1098

    Article  PubMed  CAS  Google Scholar 

  2. Karvonen M, Tuomilehto J, Libman I, LaPorte R (1993) A review of the recent epidemiological data on the worldwide incidence of type 1 (insulin-dependent) diabetes mellitus. Diabetologia 36(10):883–892

    Article  PubMed  CAS  Google Scholar 

  3. Todd JA (1999) From genome to aetiology in a multifactorial disease, type 1 diabetes. Bioessays 21(2):164–174

    Article  PubMed  CAS  Google Scholar 

  4. Xiao X, Ma B, Dong B, Zhao P, Tai N, Chen L, Wong FS, Wen L (2009) Cellular and humoral immune responses in the early stages of diabetic nephropathy in NOD mice. J Autoimmun 32(2):85–93

    Article  PubMed  CAS  Google Scholar 

  5. Nejentsev S, Cooper JD, Godfrey L, Howson JM, Rance H, Nutland S, Walker NM, Guja C, Ionescu-Tirgovişte C, Savage DA, Undlien DE, Rønningen KS, Tuomilehto-Wolf E, Tuomilehto J, Gillespie KM, Ring SM, Strachan DP, Widmer B, Dunger D, Todd JA (2004) Analysis of the vitamin D receptor gene sequence variants in type 1 diabetes. Diabetes 53:2709–2712

    Article  PubMed  CAS  Google Scholar 

  6. Norman AW, Frankel JB, Heldt AM, Grodsky GM (1980) Vitamin D deficiency inhibits pancreatic secretion of insulin. Science 209:823–825

    Article  PubMed  CAS  Google Scholar 

  7. Cantorna MT, Hayes CE, DeLuca HF (1996) 1,25-Dihydroxy vitamin D3 reversibly blocks the progression of relapsing encephalomyelitis, a model of multiple sclerosis. Proc Natl Acad Sci USA 93:7861–7864

    Article  PubMed  CAS  Google Scholar 

  8. Fan L, Tu X, Zhu Y, Zhou L, Pfeiffer T, Feltens R, Stoecker W, Zhong R (2004) Genetic association of vitamin D receptor polymorphisms with autoimmune hepatitis and primary biliary cirrhosis in the Chinese. J Gastroenterol Hepatol 20:249–255

    Article  Google Scholar 

  9. Bhalla AK, Amento EP, Serog B, Glimcher LH (1984) 1,25-Dihydroxy vitamin D inhibits antigen–induced T cell activation. J Immunol 133:1748–1754

    PubMed  CAS  Google Scholar 

  10. Ettinger RA, Liu AW, Nepom GT, Kwok WW (1998) Exceptional stability of the HLA-DQA1*0102/DQB1*0602 alpha beta protein dimer, the class II MHC molecule associated with protection from insulin-dependent diabetes mellitus. J Immunol 161:6439–6445

    PubMed  CAS  Google Scholar 

  11. Lemire JM (1995) Immunomodulatory actions of 1,25-dihydroxy vitamin D3. J Steroid Biochem Mol Biol 53:599–602

    Article  PubMed  CAS  Google Scholar 

  12. Thembleau S, Germann T, Gately MK, Adorini L (1995) The role of IL-12 in the induction of organ-specific autoimmune disease. Immunol Today 16:383–386

    Article  Google Scholar 

  13. Uitterlinden AG, Fang Y, Van Meurs JB, Pols HA, Van Leeuwen JP (2004) Genetics and biology of vitamin D receptor polymorphisms. Gene 338:143–156

    Article  PubMed  CAS  Google Scholar 

  14. Panierakis C, Goulielmos G, Mamoulakis D, Petraki E, Papavasiliou E, Galanakis E (2009) Vitamin D receptor gene polymorphisms and susceptibility to type 1 diabetes in Crete, Greece. Clin Immunol 133(2):276–281

    Article  PubMed  CAS  Google Scholar 

  15. Motohashi Y, Yamada S, Yanagawa T, Maruyama T, Suzuki R, Niino M, Fukazawa T, Kasuga A, Hirose H, Matsubara K, Shimada A, Saruta T (2003) Vitamin D receptor gene polymorphism affects onset pattern of type 1 diabetes. J Clin Endocrinol Metab 88:3137–3140

    Article  PubMed  CAS  Google Scholar 

  16. Morrison NA, Qi JC, Tokita A, Kelly PJ, Crofts L, Nguyen TV, Sambrook PN, Eisman JA (1994) Prediction of bone density from vitamin D receptor alleles. Nature 367:284–287

    Article  PubMed  CAS  Google Scholar 

  17. White C, Gardiner E, Eisman J (1998) Tissue specific and vitamin D responsive gene expression in bone. Mol Biol Rep 25(1):45–61

    Article  PubMed  CAS  Google Scholar 

  18. Carling T, Kindmark A, Hellman P, Lundgren E, Ljunghall S, Rastad J, Akerström G, Melhus H (1995) Vitamin D receptor genotypes in primary hyperparathyroidism. Nat Med 1:1309–1311

    Article  PubMed  CAS  Google Scholar 

  19. Carling T, kerstrm G, Rastad J, Westin G (1998) Vitamin D receptor and parathyroid hormone mRNA levels correspond to polymorphic VDR alleles in human parathyroid tumors. J Clin Endocrinol Metab 83:2255–2259

    Article  PubMed  CAS  Google Scholar 

  20. Ates O, Dolek B, Dalyan L, Musellim B, Ongen G, Topal-Sarikaya A (2011) The association between BsmI variant of vitamin D receptor gene and susceptibility to tuberculosis. Mol Biol Rep 38(4):2633–2636

    Article  PubMed  CAS  Google Scholar 

  21. Ban Y, Taniyama M (2001) Vitamin D receptor gene polymorphisms in Hashimoto’s thyroiditis. Thyroid 11:607–608

    Article  PubMed  CAS  Google Scholar 

  22. Guo SW, Magnuson VL, Schiller JJ, Wang X, Wu Y, Ghosh S (2006) Meta-analysis of vitamin D receptor polymorphisms and type 1 diabetes: a huge review of genetic association studies. Am J Epidemiol 164(8):711–724

    Article  PubMed  Google Scholar 

  23. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC (2007) PLINK: a tool set for whole-genome association and population based linkage analysis. Am J Hum Genet 81:559–575

    Article  PubMed  CAS  Google Scholar 

  24. Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21(2):263–265

    Article  PubMed  CAS  Google Scholar 

  25. Undlien DE, Thorsby E (2001) HLA associations in type 1 diabetes: merging genetics and immunology. Trends Immunol 22(9):467–469

    Article  PubMed  CAS  Google Scholar 

  26. Sedimbi SK, Luo XR, Sanjeevi CB, Swedish Childhood Diabetes Study Group (2007) SUMO4 M55V polymorphism affects susceptibility to type I diabetes in HLA DR3- and DR4-positive Swedish patients. Genes Immun 8(6):518–521

    Article  PubMed  CAS  Google Scholar 

  27. Ban Y, Taniyama M, Yanagawa T, Yamada S, Maruyama T, Kasuga A (2001) Vitamin D receptor initiation codon polymorphism influences genetic susceptibility to type 1 diabetes mellitus in the Japanese population. BMC Med Genet 2:7

    Article  PubMed  CAS  Google Scholar 

  28. Muller K, Bendtzen K (1992) Inhibition of human T lymphocyte proliferation and cytokine production by 1,25-dihydroxyvitamin D3. Differential effects on CD45RA+ and CD45RO+ cells. Autoimmunity 14:37–43

    Article  PubMed  CAS  Google Scholar 

  29. Rigby WF, Denome S, Fanger MW (1987) Regulation of lymphokine production and human T lymphocyte activation by 1,25-dihydroxy vitamin D3. Specific inhibition at the level of messenger RNA. J Clin Invest 79:1659–1664

    Article  PubMed  CAS  Google Scholar 

  30. D’Ambrosio D, Cippitelli M, Cocciolo MG, Mazzeo D, Di Lucia P, Lang R, Sinigaglia F, Panina-Bordignon P (1998) Inhibition of IL-12 production by 1,25-dihydroxy vitamin D3. Involvement of NF-κB downregulation in transcriptional repression of the p40 gene. J Clin Invest 101:252–262

    Article  PubMed  Google Scholar 

  31. Azarpira N, Sagheb MM, Geramizadeh B, Darai M (2009) Vitamin D receptor genotypes and kidney allograft rejection. Mol Biol Rep 36(8):2387–2392

    Article  PubMed  CAS  Google Scholar 

  32. Lee YH, Bae SC, Choi SJ, Ji JD, Song GG (2010) Associations between vitamin D receptor polymorphisms and susceptibility to rheumatoid arthritis and systemic lupus erythematosus: a meta-analysis. Mol Biol Rep

  33. Guja C, Marshall S, Welsh K, Merriman M, Smith A, Todd JA, Ionescu-Tirgoviste C (2002) The study of CTLA-4 and vitamin D receptor polymorphisms in the Romanian type 1 diabetes population. J Cell Mol Med 6:75–81

    Article  PubMed  CAS  Google Scholar 

  34. Chang TJ, Lei HH, Yeh JI, Javiel G, Cardoso H (2000) Vitamin D receptor gene polymorphisms influence susceptibility to type 1 diabetes mellitus in the Taiwanese population. Clin Endocrinol 52:575

    Article  CAS  Google Scholar 

  35. Mimbacas A, Trujillo J, Gascue C, Javiel G, Cardoso H (2007) Prevalence of vitamin D receptor gene polymorphism in a Uruguayan population and its relation to type 1 diabetes mellitus. Genet Mol Res 6(3):534–542

    PubMed  CAS  Google Scholar 

  36. Györffy B, Vásárhelyi B, Krikovszky D, Madácsy L, Tordai A, Tulassay T, Szabó A (2002) Gender-specific association of vitamin D receptor polymorphism combinations with type 1 diabetes mellitus. Eur J Endocrinol 147:803

    Article  PubMed  Google Scholar 

  37. McDermott MF, Ramachandran A, Ogunkolade BW, Aganna E, Curtis D, Boucher BJ, Snehalatha C, Hitman GA (1997) Allelic variation in the vitamin D receptor influences susceptibility to IDDM in Indian Asians. Diabetologia 40:971

    Article  PubMed  CAS  Google Scholar 

  38. Pani MA, Knapp M, Donner H, Braun J, Baur MP, Usadel KH, Badenhoop K (2000) Vitamin D receptor allele combinations influence genetic susceptibility to type 1 diabetes in Germans. Diabetes 49:504–507

    Article  PubMed  CAS  Google Scholar 

  39. Fassbender WJ, Goertz B, Weismüller K, Steinhauer B, Stracke H, Auch D, Linn T, Bretzel RG (2002) 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 34:330

    Article  PubMed  CAS  Google Scholar 

  40. Skrabic V, Zemunik T, Situm M, Terzic J (2003) Vitamin D receptor polymorphism and susceptibility to type 1 diabetes in the Dalmatian population. Diabetes Res Clin Pract 59:31

    Article  PubMed  CAS  Google Scholar 

  41. Zemunik T, Skrabic V, Boraska V, Diklic D, Terzic IM, Capkun V, Peruzovic M, Terzic J (2005) FokI polymorphism, vitamin D receptor, and interleukin-1 receptor haplotypes are associated with type 1 diabetes in the Dalmatian population. J Mol Diagn 7:600

    Article  PubMed  CAS  Google Scholar 

  42. Koeleman BP, Valdigem G, Eerligh P, Giphart MJ, Roep BO (2002) Seasonality of birth in patients with type 1 diabetes. Lancet 359:1246

    Article  PubMed  Google Scholar 

  43. Lemos MC, Fagulha A, Coutinho E, Gomes L, Bastos M, Barros L, Carrilho F, Geraldes E, Regateiro FJ, Carvalheiro M (2008) Lack of association of vitamin D receptor gene polymorphisms with susceptibility to type 1 diabetes mellitus in the Portuguese population. Hum Immunol 69(2):134–138

    Article  PubMed  CAS  Google Scholar 

  44. Bianco MG, Minicucci L, Calevo MG, Lorini R (2004) Vitamin D receptor polymorphisms: are they really associated with type 1 diabetes? Eur J Endocrinol 151(5):641–642

    Article  PubMed  CAS  Google Scholar 

  45. Casteels K, Waer M, Laureys J, Valckx D, Depovere J, Bouillon R, Mathieu C (1998) Prevention of autoimmune destruction of syngeneic islet grafts in spontaneously diabetic nonobese diabetic mice by a combination of a vitamin D3 analog and cyclosporine. Transplantation 65:1225–1232

    Article  PubMed  CAS  Google Scholar 

  46. Muntoni S, Karvonen M, Tuomilehto J (2002) Seasonality of birth in patients with type 1 diabetes. Lancet 6(359):1247–1248

    Google Scholar 

Download references

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Immunology Research Center, Buali Institute, Mashhad University of Medical Sciences, Mashhad, Iran

    Zahra Mohammadnejad, Rashin Ganjali & Sedigheh Fatemi

  2. Immunology Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Mohsen Ghanbari

  3. Associated Professor of Immunology, Immunology Research Center, Buali Institute, Mashhad University of Medical Sciences, Mashhad, Iran

    Jalil Tavakkol Afshari & Houshang Rafatpanah

  4. Postdoctoral Fellow, Department of Medicine, McMaster University, Population Health Research Institute (PHRI), Hamilton, ON, Canada

    Mahyar Heydarpour

  5. Endocrinology Department, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran

    Seyed Morteza Taghavi

Authors
  1. Zahra Mohammadnejad
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mohsen Ghanbari
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rashin Ganjali
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jalil Tavakkol Afshari
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mahyar Heydarpour
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Seyed Morteza Taghavi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sedigheh Fatemi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Houshang Rafatpanah
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Houshang Rafatpanah.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mohammadnejad, Z., Ghanbari, M., Ganjali, R. et al. Association between vitamin D receptor gene polymorphisms and type 1 diabetes mellitus in Iranian population. Mol Biol Rep 39, 831–837 (2012). https://doi.org/10.1007/s11033-011-0805-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-011-0805-3

Keywords

Search

Navigation