Coeliac disease-associated polymorphisms influence thymic gene expression.

Area of Science:

• Immunogenetics
• Molecular Biology
• Human Genetics

Background:

• Coeliac disease (CD) is associated with numerous genetic risk regions, primarily containing non-coding single nucleotide polymorphisms (SNPs).
• Previous expression quantitative trait loci (eQTL) analysis identified cis-regulatory potential for some CD-associated SNPs in peripheral blood mononuclear cells (PBMC).
• Many CD-associated regions harbor genes involved in immunological pathways, including T-cell development, which has not been extensively studied in CD pathogenesis.

Purpose of the Study:

• To investigate the regulatory potential of 50 CD-associated SNPs in thymic tissue using eQTL analysis.
• To explore the role of T-cell development pathways in CD pathogenesis.
• To identify novel thymus-specific regulatory mechanisms influenced by CD risk polymorphisms.

Main Methods:

• eQTL analysis was performed on thymic tissue samples from 42 subjects.
• Fifty CD-associated SNPs were analyzed for their association with gene expression in the thymus.
• Results were compared with existing eQTL data from PBMC and other tissues.

Main Results:

• 43 nominally significant eQTLs were identified within 24 CD-associated chromosomal regions.
• These eQTLs involved 27 expression-altering SNPs (eSNPs) and 39 unique genes (eGenes).
• Nine significant probe-SNP pairs overlapped with previous PBMC findings, while 14 eQTLs suggested potential thymus-specific regulation.

Conclusions:

• CD-associated SNPs demonstrate cis-regulatory potential within thymic tissue.
• These findings implicate T-cell development in the thymus as a potentially relevant pathway in CD pathogenesis.
• CD risk polymorphisms may exert their effects through gene regulation in the thymus, highlighting a novel aspect of CD genetics.