Endocrine Abstracts

Aim: To identify associations of polymorphisms in TLR9, IL28B, TLR2 with autoimmune adrenal insufficiency (AAI).

Methods: In n = 54 patients with AAI (isolated and as part of type 2 autoimmune polyglandular syndrome (APS-2; group 1a)), n = 9 patients with APS-1 (group 1b), n = 32 healthy individuals (group 2) we analyzed polymorphisms in IL28B (rs12979860, rs8099917), TLR9 (rs5743836, rs352140), TLR2 (rs5743708) by real-time polymerase chain reaction.

Results: In group 1, compared with group 2, a significant predominance of CT genotype of the polymorphism rs12979860 of IL28B (P = 0.010), and T allele of the rs5743836 polymorphism of TLR9 (P = 0.032) was revealed. The CC genotype of the rs12979860 polymorphism of IL28B (P = 0.025) and allele C of the rs5743836 polymorphism of TLR9 (P = 0.032) were more common in group 2 than in group 1. A comparative analysis of the distribution of haplotype frequencies of loci of IL28B (rs8099917-rs12979860) revealed that CCTT occurs significantly more frequently in group 2 compared to group 1 (P = 0.024). When comparing groups 1a and 2, significance remained only in relation to the frequencies of CT genotype of the rs12979860 polymorphism of IL28B (P = 0.024) and alleles T and C of the rs5743836 polymorphism of TLR9 (P = 0.044). In group 1b, compared with group 2, there was a predominance of CT genotype of the polymorphism rs12979860 of IL28B (P = 0.032) and the CTTT haplotype of two loci of IL28B: rs8099917 and rs12979860 (P = 0.020).

Conclusions: Patients with AAI differ from healthy individuals by a more frequent carriage of CT genotype of the polymorphic marker rs12979860 of IL28B. The T allele of the rs5743836 polymorphism of TLR9 is a prognostic marker that increases the likelihood of developing AAI, while CC genotype at the rs12979860 polymorphism of IL28B, CCTT haplotype of two loci of the IL28B (rs8099917-rs12979860) and allele C of the rs5743836 polymorphism of TLR9, perform a protective role in this disease.