Analysis of PTPN22, ZFAT and MYO9B polymorphisms in Turner Syndrome and risk of autoimmune disease

Abstract

Turner syndrome (TS) is one of the most common sexual chromosome abnormalities and is clearly associated with an increased risk of autoimmune diseases, particularly thyroid disease and coeliac disease (CD). Single-nucleotide polymorphism analyses have been shown to provide correlative evidence that specific genes are associated with autoimmune disease. Our aim was to study the functional polymorphic variants of PTPN22 and ZFAT in relation to thyroid disease and those of MYO9B in relation to CD. A cross-sectional comparative analysis was performed on Mexican mestizo patients with TS and age-matched healthy females. Our data showed that PTPN22 C1858T (considered a risk variant) is not associated with TS (X = 3.50, p = .61, and OR = 0.33 [95% CI = 0.10-1.10]). Also, ZFAT was not associated with TS (X = 1.2, p = .28, and OR = 1.22 [95% CI = 0.84-1.79]). However, for the first time, rs2305767 MYO9B was revealed to have a strong association with TS (X = 58.6, p = .0001, and OR = 10.44 [95% C = 5.51-19.80]), supporting a high level of predisposition to CD among TS patients. This report addresses additional data regarding the polymorphic variants associated with autoimmune disease, one of the most common complications in TS.

Recognition and management of adults with Turner syndrome: From the transition of adolescence through the senior years

“…No differences in the percentage of regulatory T cells have been found between girls with Turner syndrome and controls, although girls with Turner syndrome who already had autoimmune disease had a significantly lower regulatory T cell percentage (Gawlik et al, ). PTPN22, ZFAT and MYO9B polymorphisms have been studied in pediatric and adult individuals with Turner syndrome in diverse populations (Bianco et al, ; Villanueva‐Ortega et al, ). Although these areas of study help to enhance our knowledge and understanding of the possible mechanisms behind the increased risk of autoimmune disease in Turner syndrome, there is currently no clinical utility in testing for these cytokine, T cell, or genetic abnormalities.…”

Autoimmune Thyroid Disease in Specific Genetic Syndromes in Childhood and Adolescence

“…PTPN22 encodes a lymphoid-specific phosphatase which acts as a negative regulator of T cells and its polymorphisms have been linked to several autoimmune disorders. In particular, the PTPN22 C1858T polymorphism was associated with autoimmune disease risk in a Brazilian population of TS, however, these findings were not replicated in Hispanic (Mexican) TS patients (41,42), indicating the influence of different genetic backgrounds on the phenotypic expression of this polymorphism.…”

Hashimoto’s Thyroiditis and Graves’ Disease in Genetic Syndromes in Pediatric Age

“…Some studies have assessed the role of specific genes in the development of autoimmunity in TS, in particular PTPN22 that encodes a lymphoid-specific phosphatase (LYP), which is an important downregulator of T cell activation. PTPN22 C1858T polymorphism has been associated with the development of autoimmunity in a cohort of Brazilian TS subjects [127], but these findings did not emerge in the study performed by Villanueva-Ortega et al in Mexican TS girls [34].…”