title: Non-HLA autoimmunity genetic factors contributing to Autoimmune Polyglandular Syndrome type II in Tunisian patients.
abstract: Autoimmune Polyglandular Syndrome Type II (APSII) is characterized by the co-occurrence of clinical insufficiency of at least two endocrine glands. Although, HLA determinants of APSII predisposition have been identified, little attention has been paid to non-HLA genes. Here, we used SNP genotyping in a Sequenom platform and genetic association tests to study a cohort of 60 APSII Tunisian patients presenting highly frequent co-occurrence of Autoimmune Thyroid Disease (AITD) and Type 1 Diabetes (T1D) and lower frequency of Addison's disease (AD). We tested the high a priori possibility that well-established non-HLA autoimmunity loci were involved in APSII and confirmed five association signals to APSII, namely: (1) two T1D-associated SNPs, in CTLA4 and IL2RA, suggest their involvement in T1D pathogenesis in this cohort; (2) two SNPs in STAT4 and IL15 not previously associated to endocrinopathies, are possibly involved in co-occurrence of organ autoimmunity in APSII, and; (3) one SNP in TNF alpha showed association to APSII irrespective of AD. While this work was performed in a relatively small cohort, these results support the notion that the non-HLA genetic component of APSII include genetic factors specific of particular autoimmune manifestations as well as genetic factors that promote the co-occurrence of multiple autoimmune endocrinopathies.
authors.affiliation: Immunology Department, Habib Bourguiba Hospital, University of Sfax, Sfax, Tunisia. hajerfourati@yahoo.fr
authors.forename: Hajer
authors.initials: H
authors.lastname: Fourati
authors.forename: Dorra
authors.initials: D
authors.lastname: Bouzid
authors.forename: Olfa
authors.initials: O
authors.lastname: Abida
authors.forename: Najla
authors.initials: N
authors.lastname: Kharrat
authors.forename: Fatma
authors.initials: F
authors.lastname: Mnif
authors.forename: Samy
authors.initials: S
authors.lastname: Haddouk
authors.forename: Constantin
authors.initials: C
authors.lastname: Fesel
authors.forename: João
authors.initials: J
authors.lastname: Costa
authors.forename: Mourad
authors.initials: M
authors.lastname: Ben Ayed
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abid
authors.forename: Ahmed
authors.initials: A
authors.lastname: Rebai
authors.forename: Carlos
authors.initials: C
authors.lastname: Penha-Gonçalves
authors.forename: Hatem
authors.initials: H
authors.lastname: Masmoudi
mesh_terms: D000224:Addison Disease / Q000453:epidemiology* / Q000235:genetics* / Q000276:immunology; D000293:Adolescent; D000328:Adult; D015551:Autoimmunity / Q000235:genetics; D060908:CTLA-4 Antigen / Q000235:genetics; D002648:Child; D016207:Cytokines / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology* / Q000235:genetics* / Q000276:immunology; D004702:Endocrine Glands / Q000378:metabolism* / Q000473:pathology; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006680:HLA Antigens; D006801:Humans; D008297:Male; D008875:Middle Aged; D009928:Organ Specificity / Q000235:genetics; D016884:Polyendocrinopathies, Autoimmune / Q000453:epidemiology* / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D050797:STAT4 Transcription Factor / Q000235:genetics; D013967:Thyroiditis, Autoimmune / Q000453:epidemiology* / Q000235:genetics* / Q000276:immunology; D014416:Tunisia; D055815:Young Adult
chemical_list: D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D016207:Cytokines; D006680:HLA Antigens; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human