Functional SNPs in the Human Autoimmunity-Associated Locus 17q12-21
Alina S Ustiugova1,2, Kirill V Korneev3,4, Dmitry V Kuprash5,6
1Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia. ustugovaalina@yandex.ru.
Genes
|January 26, 2019
Summary
Researchers investigated single-nucleotide polymorphisms (SNPs) linked to autoimmune diseases. They identified specific SNPs, including rs12946510, that influence gene expression, potentially mediating autoimmune risk.
Area of Science:
- Genetics
- Immunology
Background:
- Genome-wide association studies (GWASes) have identified the human 17q12-21 locus as a risk region for autoimmune diseases.
- Identifying specific causative single-nucleotide polymorphisms (SNPs) within this locus remains a challenge.
Purpose of the Study:
- To functionally assess candidate SNPs within the 17q12-21 locus for their role in mediating autoimmune disease risk.
- To pinpoint specific SNPs that directly influence gene expression in relevant cell types.
Main Methods:
- Selection of six candidate SNPs in high linkage disequilibrium with known GWAS hits.
- Luciferase reporter assays were performed in leukocytic cell lines to evaluate SNP functionality.
- Bioinformatic predictions were used to assess the impact of SNPs on transcription factor binding sites.
Main Results:
- Four SNPs (rs12946510, rs4795397, rs12709365, and rs8067378) demonstrated significant influence on reporter gene expression.
- SNP rs12946510 exhibited the strongest effect across three different cell types.
- rs12946510 is predicted to alter binding sites for transcription factors MEF2A/C and FOXO1.
Conclusions:
- Specific SNPs in the 17q12-21 locus, notably rs12946510, possess functional regulatory activity.
- These findings suggest that rs12946510 may play a direct role in the pathogenesis of autoimmune diseases by modulating gene expression.
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