Association of the CYP27B1 C(-1260)A Polymorphism with Autoimmune Addison's Disease

Autoimmune Addison's disease (AAD) is a complex endocrine disorder with several susceptibility loci. This study was aimed to investigate the associations of CYP27B1 C(- 1260) A and PDCD1 G7146A polymorphisms with AAD in a Polish cohort, comprising 101 AAD patients and 251 healthy controls. CYP27B1 encodes 1alpha-hydroxylase, responsible for conversion of the vitamin D-3 precursor into its active form, involved in the immune function. PDCD1 gene gives rise to an inhibitory immune receptor, expressed on activated lymphocytes. Polymorphic variants of these genes had previously been associated with various autoimmune disorders. Genotyping was performed by PCR-RFLP method. The CYP27B1 C(- 1260) allele appeared significantly more frequent in AAD compared to controls (p = 0.020), yielding an OR of 1.53 (95% CI 1.07-2.19). The distribution of C(- 1260)A genotypes also demonstrated significant difference (p = 0.003). Stratification according to the presence of concomitant autoimmune disorders revealed an association of the C(- 1260) allele with the polyendocrine cases of AAD (p = 0.031), while no significance was found for the isolated ADD compared with healthy controls (p = 0.253). Overall, the association between AAD and C(- 1260)A was confirmed in a meta-analysis of 325 AAD patients and 952 controls from three different European populations. Under a fixed-effect model, C(- 1260) allele and CC genotype were associated with AAD susceptibility with a pooled OR of 1.44 (95% CI 1.18-1.75) and 1.88 (95% CI 1.42-2.36), respectively. No differences were observed for the PDCD1 G7146A between affected subjects and controls (p > 0.05). In conclusion, this study confirms the association of the CYP27B1 C(- 1260)A polymorphism with AAD, whereas the contribution of PDCD1 G7146A seems less likely.