PTPN22 and CTLA-4 Polymorphisms are Associated with Polyglandular Autoimmunity.

PTPN22 and CTLA-4 Polymorphisms are Associated with Polyglandular Autoimmunity.

J Clin Endocrinol Metab. 2018 Feb 01;:

Authors: Houcken J, Degenhart C, Bender K, König J, Frommer L, Kahaly GJ

Abstract
Context: Single nucleotide polymorphisms (SNP) of various genes increase susceptibility to monoglandular autoimmunity. Scarce data are available in autoimmune polyglandular syndromes (APS).
Objective: Evaluate potential associations of eight SNP with APS.
Setting: Academic referral endocrine clinic.
Patients: A total of 543 patients with APS, monoglandular autoimmunity and controls.
Intervention: The SNP protein tyrosine phosphatase non-receptor type 22 (PTPN22) rs2476601 (+1858), cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) rs3087243 (CT60) and rs231775 (AG49), Vitamin D Receptor (VDR) rs1544410 (Bsm I), rs7975232 (Apa I), rs731236 (Taq I), tumor necrosis factor alpha rs1800630 (-863) and Interleukin-2 receptor alpha rs10795791 were tested by single base extension in all subjects.
Results: The PTPN22 +1858 allele and genotype distribution were markedly different between APS, type 1 diabetes (T1D) OR 2.67, 95% CI 1.52-4.68, p=0.001, Graves' disease (GD), OR 1.94, 1.16-3.25, p=0.011, and controls OR 3.31, 1.82-6.02, p<0.001. T-allele carriers risk for APS was increased (OR 3.76, 1.97-7.14, p<0.001). T-allele frequency was higher among APS compared to controls (OR 3.25, 1.82-5.82, p<0.001), T1D (OR 2.54, 1.48-4.36, p=0.001) or GD (OR 1.89, 1.15-3.11, p=0.012). The SNP CTLA-4 CT60 G-allele carriers were more frequent in APS (85%) than controls (78%) OR 1.55, 0.81-2.99. Combined analysis of CTLA-4 AG49 and CT60 revealed an OR 4.89, 1.86-13.59, p=0.00018 of the genotype combination AG/GG for APS versus controls. VDR polymorphisms Bsm I, Apa I and Taq I did not, but the haplotypes differed between APS and controls (p=0.0011).
Conclusions: PTPN22 and CTLA-4 polymorphisms are associated with APS and differentiate between polyglandular and monoglandular autoimmunity.

PMID: 29409002 [PubMed - as supplied by publisher]

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