Study of polymorphisms in CTLA-4, PTPN22 and IFIH1 genes in children and teenagers with autoimmune thyroid disorders (Graves disease and Hashimoto thyroiditis) associated to DM type 1

• Grant number: 09/17327-7
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2011
• End date: April 30, 2013
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Suemi Marui
• Grantee: Suemi Marui
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Graves´ disease and Hashimoto thyroiditis are autoimmune thyroid disorders (AITD) with appearance eventually in infancy and with a slightly higher incidence in adolescence. Clinical manifestations so early can be determined by environmental and genetic factors. Among genetic factors CTLA-4 and PTPN22 genes seem to be enrolled. CTLA-4 polymorphisms are frequently studied, but in a Brazilian pediatric population, this association was not evident based on the only A49G polymorphism studied. The R2620W polymorphism of PTPN22 gene also seems to be associated to development of Graves´ disease in different ethnic populations. It is noteworthy that CTLA4 and PTPN22 polymorphisms are described as risk factors to type 1 Diabetes Mellitus (DM1), independently of HLA. Therefore, autoimmune thyroid disease and DM1 can share the same genetic background. Recently A946T polymorphism of interferon-induced helicase (IFIH1) gene was described in association to DM1, due to possible viral infection role in disease development. The IFIH1 gene codifies a protein that triggers apoptosis of RNA viral infected cells. In Graves´ disease, viral infection role is doubtfully. However, A946T polymorphism of IFIH1 gene seems to be associated to Graves´ disease development. Symptoms surge of AITD in childhood and adolescence can be related to a different genetic background than adulthood, commonly studied, particularly if AITD is associated to other autoimmune disease, such as DM1. Therefore to determine if exists the participation of genes enrolled in autoimmune tolerance in AITD and in patients with DM1 and AITD will bring new knowledge to this special population characterized by precocious surge of autoimmune disease, such as the pediatric population. (AU)