Vitamin D receptor gene polymorphism: association with Crohn's disease susceptibility

J D Simmons, C Mullighan, K I Welsh, D P Jewell, J D Simmons, C Mullighan, K I Welsh, D P Jewell

Abstract

Background: The vitamin D receptor (VDR) gene represents a strong positional candidate susceptibility gene for inflammatory bowel disease (IBD). The VDR gene maps to a region on chromosome 12 that has been shown to be linked to IBD by genome screening techniques. It is the cellular receptor for 1,25(OH)(2) vitamin D(3) (calcitriol) which has a wide range of different regulatory effects on the immune system. IBD is characterised by activation of the mucosal immune system.

Aim: To determine if polymorphisms in the VDR gene are associated with susceptibility to IBD SUBJECTS: European Caucasoids: 158 patients with ulcerative colitis, 245 with Crohn's disease, and 164 cadaveric renal allograft donor controls.

Method: Single nucleotide polymorphisms (TaqI, ApaI, and FokI) in VDR were typed in patients with Crohn's disease, ulcerative colitis, and controls by polymerase chain reaction with sequence specific primers.

Results: There were significantly more homozygotes for the TaqI polymorphism at codon 352 of exon 8 (genotype "tt") among patients with Crohn's disease (frequency 0.22) than patients with ulcerative colitis (0.12) or controls (0.12) (odds ratio 1.99; 95% confidence interval 1.14-3.47; p=0.017).

Conclusion: This study provides preliminary evidence for a genetic association between Crohn's disease susceptibility and a gene that lies within one of the candidate regions determined by linkage analysis.

References

    1. Science. 1983 Sep 16;221(4616):1181-3
    1. J Infect Dis. 1999 Mar;179(3):721-4
    1. Immunology. 1986 Jan;57(1):159-63
    1. Nucleic Acids Res. 1988 Feb 11;16(3):1215
    1. Proc Natl Acad Sci U S A. 1988 May;85(10):3294-8
    1. Nucleic Acids Res. 1991 Jul 11;19(13):3561-7
    1. Nature. 1994 Jan 20;367(6460):284-7
    1. J Nutr. 1995 Jun;125(6 Suppl):1690S-1694S
    1. Nat Genet. 1996 Oct;14(2):199-202
    1. J Bone Miner Res. 1996 Dec;11(12):1850-5
    1. J Natl Cancer Inst. 1997 Jan 15;89(2):166-70
    1. J Bone Miner Res. 1997 May;12(5):726-33
    1. Biochem Biophys Res Commun. 1997 Sep 8;238(1):77-80
    1. J Clin Invest. 1998 Jan 1;101(1):252-62
    1. Annu Rev Immunol. 1998;16:593-617
    1. Am J Hum Genet. 1998 Jul;63(1):95-100
    1. Annu Rev Nutr. 1998;18:233-58
    1. Gastroenterology. 1998 Nov;115(5):1066-71
    1. J Infect Dis. 1999 Jan;179(1):187-91
    1. Gut. 1998 Dec;43(6):735-6
    1. Biochem Biophys Res Commun. 1985 Mar 15;127(2):596-603

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