Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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Advances in Clinical and Experimental Medicine

2007, vol. 16, nr 4, July-August, p. 549–559

Publication type: review article

Language: English

The Molecular Background of Autoimmune Endocrine Disorders

Molekularne podłoże chorób autoimmunologicznych układu dokrewnego

Marta Fichna1,, Magdalena Żurawek2,

1 Department of Endocrinology, Metabolism, and Internal Diseases, Poznań University of Medical Sciences, Poland

2 Department of Molecular Pathology, Institute of Human Genetics, Polish Academy of Sciences, Poznań, Poland

Abstract

Recent data concerning the molecular background of autoimmune endocrine disorders are presented. Apart from a few rare syndromes caused by single gene mutations, most endocrine autoimmune diseases are complex polygenic traits triggered by environmental factors. The search for the genetic component concentrates on polymorphisms in genes involved in immune tolerance and immune response. The DNA polymorphisms may result from single nucleotide substitutions (SNPs) or from a variable number of tandem repeats of a short sequence, as in the IDDM2 locus associated with type 1 diabetes. The HLA system, especially class II, was the first confirmed source of alleles conferring susceptibility to autoimmune disorders. Currently, major attention is turning to numerous SNPs which may influence the structure or function of proteins taking part in immune mechanisms. Polymorphisms in CTLA−4, PTPN22, PDCD1, FCRL3, and SUMO4 as well as those in genes associated with vitamin D action have been hitherto investigated. Some of these have shown significant association with type 1 diabetes, Graves’ disease, chronic thyroiditis, and/or autoimmune Addison’s disease. There are now many other gene polymorphisms under investigation in autoimmune endocrine disorders. The progressing exploration of this field will enable future practical use in forecasting the development of autoimmune disorders and possibly in preventing their onset.

Streszczenie

Artykuł w skrócie przedstawia aktualne dane dotyczące molekularnego podłoża autoimmunologicznych chorób układu dokrewnego. Poza kilkoma rzadkimi zespołami spowodowanymi mutacjami pojedynczego genu, większość autoimmunologicznych chorób endokrynnych jest mutacją wielu genów, ujawniającą się pod wpływem czynników środowiskowych. Poszukiwania składowej genetycznej koncentrują się na polimorfizmach genów zaangażowanych w procesy tolerancji immunologicznej i odpowiedź odpornościową. Polimorfizmy DNA mogą być skutkiem zmian jednonukleotydowych albo różnej liczby tandemowych powtórzeń krótkiej sekwencji, jak w przypadku locus IDDM2, sprzężonego z cukrzycą typu 1. Układ HLA, zwłaszcza klasy II, był pierwszym potwierdzonym źródłem allelów sprzyjających rozwojowi zaburzeń autoimmunizacyjnych. Obecnie uwagę skupiają liczne polimorfizmy jednonukleotydowe mogące wpływać na strukturę i funkcję białek biorących udział w mechanizmach immunologicznych. Dotychczas badano polimorfizmy genów CTLA−4, PTPN22, PDCD1, FCRL3, SUMO4, a także genów związanych z działaniem witaminy D w organizmie. Niektóre z nich wykazały znaczący związek z rozwojem cukrzycy typu 1, choroby Graves−Basedowa, przewlekłego zapalenia tarczycy i/lub choroby Addisona. Obecnie w autoimmunologicznych chorobach układu dokrewnego analizuje się różne polimorfizmy genetyczne. Ich coraz lepsza znajomość umożliwi w przyszłości zastosowanie praktyczne – przewidywanie ryzyka chorób autoimmunologicznych i, być może – zapobieganie ich rozwojowi.

Key words

autoimmunity, polymorphism, endocrinology

Słowa kluczowe

autoimmunizacja, polimorfizm, endokrynologia

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