Endocrine Abstracts (2010) 22 P26

Confirmation of vitamin D receptor polymorphism TaqI and detection of a new single nucleotide polymorphism (SNP) in the CTLA4-region (CTLA4-CT60) as susceptibility markers for Addison's disease

Gesine Meyer1, Elizabeth Ramos-Lopez1, Marissa Penna-Martinez1, Heinrich Kahles1, Holger Willenberg2 & Klaus Badenhoop1

1Internal Medicin I, Department of Endocrinology and Diabetes, University Hospital Frankfurt, Frankfurt, Germany; 2Clinic for Endocrinology, University Hospital Duesseldorf, Duesseldorf, Germany.

Objective: Addison’s disease (AD) is a rare and complex endocrine disorder. Genetic susceptibility loci known so far are predominantly shared with other, more frequent autoimmune endocrinopathies. We therefore investigated polymorphisms of the CTLA4-region, the vitamin D system (vitamin D receptor VDR, CYP24 and CYP27B1 gene) as well as cytokine CXCL10 gene for their association in AD.

Methods: Patients with AD (n=203) and healthy controls (n=746) were genotyped for polymorphisms of VDR (ApaI, BsmI, FokI, TaqI), CYP27B1 hydroxylase gene (CYP27B1 C(−1260)A, CYP-1a-Intron 6, CYP2R1-57), CYP24 gene (CYP 24-26, CYP24-rs2248137, CYP24-rs2296241), vitamin D binding protein gene (DBP DBP-HaeIII-rs7041, DBP-Sty-rs4458), the CTLA-4 gene region (CTLA4-A/G, CTLA4-1661G, CTLA4-CT60, CTLA4-24HM30, CTLA4–PR) and CXCL10 gene (CXCL10-90, CXCL10-89).

Results: VDR polymorphism TaqI allele t as well as the CTLA4-region SNP CTLA4-CT60 allele g were significantly more frequent in patients with AD compared with healthy controls (43.3 vs 35.9%, P=0.02 respectively 67 vs 57%, P=0.012).

We could not find any significant differences in the other examined polymorphisms including CYP27B1 C(−1260)A (P=0.4).

Conclusions: Investigating an extended number of German patients we confirm an association of VDR polymorphism TaqI and AD. There was no association of the CYP27B1 promoter polymorphism C(−1260)A in contrast to previous findings.

The CTLA4-region SNP CTLA4-CT60 however is significantly associate with AD which we also find similarly in Graves’s disease, AIH as well as type 1 diabetes.

Owing to the high prevalence in the population these genetic susceptibility markers appear to be neither distinctive nor predictive of AD but may unravel pathophysiological pathways suitable for immune intervention.

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