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J Clin Endocrinol Metab. 2018 May 1;103(5):1977-1984. doi: 10.1210/jc.2017-02577.

PTPN22 and CTLA-4 Polymorphisms Are Associated With Polyglandular Autoimmunity.

Author information

Molecular Thyroid Research Laboratory, Johannes Gutenberg University Medical Center, Mainz, Germany.
Institute of Legal Medicine, Johannes Gutenberg University Medical Center, Mainz, Germany.
Institute of Medical Biostatistics, Epidemiology and Informatics, Johannes Gutenberg University Medical Center, Mainz, Germany.



Single nucleotide polymorphisms (SNPs) of various genes increase susceptibility to monoglandular autoimmunity. Data on autoimmune polyglandular syndromes (APSs) are scarce.


Evaluate potential associations of eight SNPs with APSs.


Academic referral endocrine clinic.


A total of 543 patients with APS and monoglandular autoimmunity and controls.


The SNP protein tyrosine phosphatase nonreceptor 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 α rs1800630 (-863); and interleukin-2 receptor alpha rs10795791 were tested by single-base extension in all subjects.


The PTPN22 +1858 allele and genotype distribution were markedly different between APS, type 1 diabetes [T1D; odds ratio (OR): 2.67; 95% confidence interval (CI): 1.52 to 4.68; P = 0.001], Graves disease (GD; OR: 1.94; 95% CI: 1.16 to 3.25; P = 0.011), and controls (OR: 3.31, 95% CI: 1.82 to 6.02; P < 0.001). T-allele carriers' risk for APS was increased (OR: 3.76; 95% CI: 1.97 to 7.14; P < 0.001). T-allele frequency was higher among APS than controls (OR: 3.25; 95% CI: 1.82 to 5.82; P < 0.001), T1D (OR: 2.54; 95% CI: 1.48 to 4.36; P = 0.001), or GD (OR: 1.89; 95% CI: 1.15 to 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; 95% CI: 0.81 to 2.99). Combined analysis of CTLA-4 AG49 and CT60 revealed OR 4.89; 95% CI: 1.86 to13.59; P = 0.00018 of the genotype combination AG/GG for APS vs controls. VDR polymorphisms Bsm I, Apa I, and Taq I did not, but the haplotypes differed between APS and controls (P = 0.0011).


PTPN22 and CTLA-4 polymorphisms are associated with APS and differentiate between polyglandular and monoglandular autoimmunity.

[Indexed for MEDLINE]

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