Involvement of HCP5 polymorphism in age at onset of Graves' disease

• Grant number: 24/22801-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2025
• End date: January 31, 2026
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Suemi Marui
• Grantee: Sofia Zoéga Andreatta Coelho
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Graves' disease (GD) is an autoimmune disease characterized by the presence of antibodies against the TSH receptor (TRAb), causing hyperthyroidism and diffuse goiter. Some patients may present with Graves' ophthalmopathy (GO) and, more rarely, dermatopathy. GD affects more women in their 3rd and 5th decades of life, and is rare in childhood and the elderly. Treatment consists of the use of antithyroid drugs (ATD), radioiodine therapy or total thyroidectomy. The choice and response to each of these depends on the severity of hyperthyroidism and GO, size of the goiter, patient preference, available resources and age of onset. Children present with more severe clinical symptoms without GO and less response to ATD, while the elderly have milder symptoms, with moderate to severe GO. Genetic factors, such as polymorphisms in the CTLA4, PTPN22, TSHR genes, among many others, have already been associated with GD in different populations. The rs3094228 polymorphism in HCP5 gene, located in MHC class I, is associated with susceptibility to several autoimmune diseases. This gene encodes a long non-coding RNA expressed in immune cells, influencing cytotoxicity and the autoimmune response. Recent studies have associated the C allele of rs3094228 with early onset of GD, suggesting that HCP5 may be a key factor in the etiology and progression of GD. Understanding the genetic mechanisms in different age groups is essential for the development of personalized strategies. With this research, we will be able to evaluate the influence of this variant on the presentation of GD in patients of different ages, including the elderly, who are underrepresented in previous studies.