A missense single-nucleotide polymorphism in the sialic acid acetylesterase (SIAE) gene is associated with anti-PIT-1 antibody syndrome.

Abstract

A novel clinical entity related to autoimmune polygladular syndrome (APS) termed "anti-PIT-1 antibody syndrome" is characterized by a presence of circulating autoantibody against the pituitary-specific transcriptional factor-1 (PIT-1) with acquired specific defect in GH, PRL, and TSH. Although autoimmunity to PIT-1 has been suggested, the underlying mechanisms remain to be elucidated. Sialic acid acetylesterase (SIAE) plays a crucial role in regulating the threshold of autoantibody production of B-cells and the defective variants of SIAE are associated with an increased risk of various autoimmune diseases such as type 1 diabetes (T1DM). To explore the link between anti-PIT-1 antibody syndrome and SIAE, we analyzed SIAE gene in 3 patients with anti-PIT-1 antibody syndrome and 200 healthy control subjects, and compared the prevalence of single nucleotide polymorphisms. Intriguingly, we found A467V SIAE variants (c.1400C>T, rs7941523) in a heterozygous state in all the patients with anti-PIT-1 antibody syndrome, while we detected in 6 % of control subjects, in which the prevalence was significantly increased in the patients (P<0.0005). Considering the physiological function of SIAE and the clinical features of anti-PIT-1 antibody syndrome, present data imply a novel aspect of the pathogenesis in this disease.

• Authors: Masaaki Yamamoto, Genzo Iguchi, Hironori Bando, Hidenori Fukuoka, Kentaro Suda, Michiko Takahashi, Hitoshi Nishizawa, Ryusaku Matsumoto, Katsuyoshi Tojo, Atsuko Mokubo, Tsutomu Ogata, Yutaka Takahashi
• Journal: Endocrine journal (Endocr J) Vol. 61 Issue 6 Pg. 641-4 ( 2014) ISSN: 1348-4540 [Electronic] Japan
• PMID: 24748456 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantibodies
• Transcription Factor Pit-1
• Acetylesterase
• sialate O-acetylesterase

Topics

• Acetylesterase (genetics)
• Aged
• Aged, 80 and over
• Amino Acid Substitution
• Autoantibodies (blood, genetics)
• Autoimmune Diseases (genetics, immunology)
• Case-Control Studies
• Humans
• Male
• Middle Aged
• Mutation, Missense
• Pituitary Diseases (genetics, immunology)
• Polymorphism, Single Nucleotide
• Syndrome
• Transcription Factor Pit-1 (immunology)