Analysis of the autoimmune regulator gene in patients with autoimmune non-APECED polyendocrinopathies

Genomics. 2013 Sep;102(3):163-8. doi: 10.1016/j.ygeno.2013.04.016. Epub 2013 Apr 30.


The pathogenesis of autoimmunity was derived from a complex interaction of genetic and environmental factors. Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy is a rare autosomal recessive disease caused by mutations in the autoimmune regulator (AIRE) gene. AIRE gene variants and, in particular, heterozygous loss-of-function mutations were also discovered in organ-specific autoimmune disorders, possibly contributing to their etiopathogenesis. It was suggested that even predisposition to develop certain autoimmune conditions may be derived from AIRE gene polymorphisms including S278R and intronic IVS9+6 G>A. In this study we unravel the hypothesis on whether AIRE gene variants may predispose individuals to associated autoimmune conditions in 41 Italian patients affected by non-APECED autoimmune polyendocrinopathies. We could not detect any heterozygous mutations of the AIRE gene. Although a trend of association was observed, heterozygous polymorphisms S278R and IVS9+6 G>A were detected in patients without statistically significant prevalence than in controls. Their putative contribution to autoimmune polyendocrinopathies and their predictive value in clinical strategies of disease development could be unravelled by analysing a larger sample of diseased patients and healthy individuals.

Keywords: (INSM2) protein tyrosine phosphatase insulinoma associated antigen 2; (NLRP5) leucine-rich-repeat protein 5; (TGM) transglutaminase; ACA; ACTH; AIH; AIRE; AMA; ANA; ANCA; APECED; APS1; ASMA; AU; CD; DNA; ENA; GADA; GWA; HT; Hashimoto's thyroiditis; IA2; IAA; ICA; IFNω; MC; Mutation; NALP5; OMIM; Online Mendelian Inheritance in Man; PBC; PCA; PCR; PHD; PSC; Polyendocrinopathy; Polymorphism; RIA; RNA; RT-PCR; SNPs; SSc; T1D; TG; TPO; TRG; Type 1 diabetes; adrenal cortex antibodies; adrenocorticotropic hormone; alopecia universalis; anti-LC1 Abs; anti-LKM; anti-glutamic acid decarboxylase (isoform 65) autoantibodies; anti-insulin antibodies; anti-mitochondrial antibodies; anti-neutrophil cytoplasmic antibodies; anti-nuclear antibodies; anti-smooth muscle antibodies; autoimmune hepatitis; autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome; autoimmune polyglandular syndrome Type 1; autoimmune regulator; cDNA; celiac disease; complementary deoxyribonucleic acid; deoxyribonucleic acid; double stranded DNA; dsDNA; extractable nuclear antigens; genome wide association; interferon ω; islet cell antibodies; liver cytosol Type 1 antibodies; liver–kidney microsomal antibodies; mucocutaneous candidiasis; parietal cell antibodies; plant homeo domain; polymerase chain reaction; primary biliary cirrhosis; primary sclerosing cholangitis; radioimmunoassay; reverse transcriptase PCR; ribonucleic acid; single nucleotide polymorphisms; systemic sclerosis; thyroglobulin; thyroperoxidase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Case-Control Studies
  • Child
  • Female
  • Genetic Carrier Screening
  • Humans
  • Italy
  • Male
  • Polyendocrinopathies, Autoimmune / genetics*
  • Polyendocrinopathies, Autoimmune / metabolism
  • Polymorphism, Genetic*
  • Sequence Analysis, DNA
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Young Adult


  • APECED protein
  • Transcription Factors