PTPN22 and CTLA-4 Polymorphisms Are Associated With Polyglandular Autoimmunity
| Autor: | Juliane Houcken, Christina Degenhart, Lara Frommer, George J. Kahaly, Klaus Bender, Jochem König |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Adult
Male 0301 basic medicine medicine.medical_specialty Genotype Endocrinology Diabetes and Metabolism Graves' disease Clinical Biochemistry 030209 endocrinology & metabolism Single-nucleotide polymorphism Polymorphism Single Nucleotide Biochemistry Calcitriol receptor PTPN22 Young Adult 03 medical and health sciences 0302 clinical medicine Endocrinology Gene Frequency Internal medicine medicine Humans CTLA-4 Antigen Genetic Predisposition to Disease Polyendocrinopathies Autoimmune Allele frequency Genetic Association Studies business.industry Biochemistry (medical) Haplotype Case-control study Protein Tyrosine Phosphatase Non-Receptor Type 22 Odds ratio Middle Aged medicine.disease 030104 developmental biology Case-Control Studies Female business |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 103:1977-1984 |
| ISSN: | 1945-7197 0021-972X |
| Popis: | Context Single nucleotide polymorphisms (SNPs) of various genes increase susceptibility to monoglandular autoimmunity. Data on autoimmune polyglandular syndromes (APSs) are scarce. Objective Evaluate potential associations of eight SNPs with APSs. Setting Academic referral endocrine clinic. Patients A total of 543 patients with APS and monoglandular autoimmunity and controls. Intervention 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. Results 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). Conclusions PTPN22 and CTLA-4 polymorphisms are associated with APS and differentiate between polyglandular and monoglandular autoimmunity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|