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Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry
Published on: June 21, 2018
Relationship between SNPs and expression level for candidate genes in rheumatoid arthritis
M Fodil1, V H Teixeira, V Chaudru
1GenHotel-EA3886, Evry-Val d'Essonne University, Evry-Genopole , France.
Genetic analysis of rheumatoid arthritis (RA) identified a link between RNASE2 gene expression and a specific polymorphism. However, family-based association tests did not confirm a direct genetic link for candidate genes in RA patients.
Area of Science:
- Genetics
- Immunology
- Molecular Biology
Background:
- Identifying genetic variants is crucial for understanding multifactorial diseases like rheumatoid arthritis (RA).
- Previous transcriptomic studies highlighted six genes with differential expression between RA patients and controls.
Purpose of the Study:
- To investigate the role of single nucleotide polymorphisms (SNPs) in six candidate genes in the context of rheumatoid arthritis (RA).
- To evaluate the association between gene expression levels and specific genotypes in RA patients.
Main Methods:
- Genotyping of 10 SNPs in six genes (S100A8, RNASE2, PGLYRP1, RUNX3, IL2RB, LY96).
- Analysis of gene expression and SNP genotype relationships using Kruskal-Wallis and Mann-Whitney tests.
- Family-based association tests in trio families for genetic association studies.
Main Results:
- A relationship was observed between RNASE2 gene expression and rs2013109 genotypes in a small cohort of RA patients (p = 0.030).
- A significant association between PGLYRP1-rs2041992 and RA was found in a French discovery sample (p = 0.019), particularly in patients with the HLA-DRB1 shared epitope.
- This association was not replicated in a larger European sample (p = 0.6).
Conclusions:
- Family-based association tests did not establish a significant genetic association between the tested SNPs and rheumatoid arthritis (RA).
- Differential expression of RNASE2 in RA patients was linked to a sequence polymorphism, suggesting potential disease-specific regulation.
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