Objective: Addisons 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, CTLA4PR) 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 Gravess 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.
Prague, Czech Republic
24 - 28 Apr 2010
European Society of Endocrinology