학술논문
Genome-Wide Analysis Identifes Two Susceptibility Loci for Positive Thyroid Peroxidase and Thyroglobulin Antibodies
CLINICAL RESEARCH ARTICLE
CLINICAL RESEARCH ARTICLE
Document Type
Report
Author
Source
Journal of Clinical Endocrinology & Metabolism. March 2020, Vol. 105 Issue 3, p944, 8 p.
Subject
Language
English
ISSN
0021-972X
Abstract
Thyroid peroxidase (TPO) and thyroglobulin (Tg) are main components of the thyroid gland and play an important role in the production of thyroid hormones (1). The development of antibodies to [...]
Introduction: Thyroid peroxidase (TPO) and thyroglobulin (Tg) are main components of the thyroid gland and play an essential role in thyroid hormone synthesis. The development of antibodies to thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) is the major diagnostic hallmark and early indicator of autoimmune thyroid disease. TPOAb and TgAb are under strong genetic infuence; however, genetic factors that determine thyroid antibody positivity are largely unknown. Materials and Methods: To identify novel loci associated with TPOAb and/or TgAb positivity, we performed a genome-wide meta-analysis in a total of 2613 individuals from Croatia. Participants with elevated plasma TPOAb and/or TgAb were defined as cases (N = 619) and those with TPOAb and TgAb within reference values were defined as controls (N = 1994). Results: We identified 2 novel loci, of which 1 is located within the YES1 gene (rs77284350, P = 1.50 * 10 (-8) ), and the other resides within the IRF8 gene (rs16939945, P = 5.04 * 10 (-8) ). Conclusions: Although the observed variants were associated with TPOAb and TgAb positivity for the first time, both YES1 and IRF8 were previously linked to susceptibility to other autoimmune diseases, and represent plausible biological candidates. This study adds to the knowledge of genetics underlying thyroid antibodies and provides a good basis for further research. (J Clin Endocrinol Metab 105: 944-951, 2020) Key Words: genome-wide association study, meta-analysis, thyroid peroxidase antibody, thyroglobulin antibody
Introduction: Thyroid peroxidase (TPO) and thyroglobulin (Tg) are main components of the thyroid gland and play an essential role in thyroid hormone synthesis. The development of antibodies to thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) is the major diagnostic hallmark and early indicator of autoimmune thyroid disease. TPOAb and TgAb are under strong genetic infuence; however, genetic factors that determine thyroid antibody positivity are largely unknown. Materials and Methods: To identify novel loci associated with TPOAb and/or TgAb positivity, we performed a genome-wide meta-analysis in a total of 2613 individuals from Croatia. Participants with elevated plasma TPOAb and/or TgAb were defined as cases (N = 619) and those with TPOAb and TgAb within reference values were defined as controls (N = 1994). Results: We identified 2 novel loci, of which 1 is located within the YES1 gene (rs77284350, P = 1.50 * 10 (-8) ), and the other resides within the IRF8 gene (rs16939945, P = 5.04 * 10 (-8) ). Conclusions: Although the observed variants were associated with TPOAb and TgAb positivity for the first time, both YES1 and IRF8 were previously linked to susceptibility to other autoimmune diseases, and represent plausible biological candidates. This study adds to the knowledge of genetics underlying thyroid antibodies and provides a good basis for further research. (J Clin Endocrinol Metab 105: 944-951, 2020) Key Words: genome-wide association study, meta-analysis, thyroid peroxidase antibody, thyroglobulin antibody