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Association Between STAT4 rs7574865 Polymorphism and Rheumatoid Arthritis: Debate Unresolved.

ABSTRACT: Background:STAT4 rs7574865 polymorphism has been evidently associated with susceptibility to Rheumatoid Arthritis (RA) in European and Eastern Asian populations, whereas studies in other countries reported otherwise. Objective:We investigated the distribution of STAT4 rs7574865 polymorphism in a group of Syrian RA patients. Methods:Eighty-one RA patients and forty healthy controls were enrolled and STAT4 rs7574865 was genotyped by direct sequencing. RA patients were stratified according to Anti-Citrullinated Protein Antibodies (ACPA) status for analysis. Results:Minor T allele frequencies were 30.4%, 16.7%, and 23.8% in ACPA-positive RA patients, ACPA-negative RA patients, and healthy controls, respectively. No significant differences in STAT4 rs7574865 allele/genotype frequencies were found between ACPA-positive RA patients, ACPA-negative RA patients, and healthy controls (P>0.05). Conclusion:STAT4 rs7574865 TT genotype showed a potential impact on ACPA positivity in Syrian RA patients. However, STAT4 rs7574865 effect on RA onset and severity is minor compared to other genetic factors such as HLA-DRB1 shared epitope alleles.

SUBMITTER: Tarakji I

PROVIDER: S-EPMC6210524 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Association Between <i>STAT4</i> rs7574865 Polymorphism and Rheumatoid Arthritis: Debate Unresolved.

Tarakji Iman I Habbal Wafa W Monem Fawza F

The open rheumatology journal 20181024

<h4>Background</h4><i>STAT4</i> rs7574865 polymorphism has been evidently associated with susceptibility to Rheumatoid Arthritis (RA) in European and Eastern Asian populations, whereas studies in other countries reported otherwise.<h4>Objective</h4>We investigated the distribution of <i>STAT4</i> rs7574865 polymorphism in a group of Syrian RA patients.<h4>Methods</h4>Eighty-one RA patients and forty healthy controls were enrolled and <i>STAT4</i> rs7574865 was genotyped by direct sequencing. RA ...[more]

PMID: 30505369

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Project description:BackgroundRheumatoid arthritis is a chronic inflammatory disease with a substantial genetic component. Susceptibility to disease has been linked with a region on chromosome 2q.MethodsWe tested single-nucleotide polymorphisms (SNPs) in and around 13 candidate genes within the previously linked chromosome 2q region for association with rheumatoid arthritis. We then performed fine mapping of the STAT1-STAT4 region in a total of 1620 case patients with established rheumatoid arthritis and 2635 controls, all from North America. Implicated SNPs were further tested in an independent case-control series of 1529 patients with early rheumatoid arthritis and 881 controls, all from Sweden, and in a total of 1039 case patients and 1248 controls from three series of patients with systemic lupus erythematosus.ResultsA SNP haplotype in the third intron of STAT4 was associated with susceptibility to both rheumatoid arthritis and systemic lupus erythematosus. The minor alleles of the haplotype-defining SNPs were present in 27% of chromosomes of patients with established rheumatoid arthritis, as compared with 22% of those of controls (for the SNP rs7574865, P=2.81x10(-7); odds ratio for having the risk allele in chromosomes of patients vs. those of controls, 1.32). The association was replicated in Swedish patients with recent-onset rheumatoid arthritis (P=0.02) and matched controls. The haplotype marked by rs7574865 was strongly associated with lupus, being present on 31% of chromosomes of case patients and 22% of those of controls (P=1.87x10(-9); odds ratio for having the risk allele in chromosomes of patients vs. those of controls, 1.55). Homozygosity of the risk allele, as compared with absence of the allele, was associated with a more than doubled risk for lupus and a 60% increased risk for rheumatoid arthritis.ConclusionsA haplotype of STAT4 is associated with increased risk for both rheumatoid arthritis and systemic lupus erythematosus, suggesting a shared pathway for these illnesses.

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Association Between STAT4 rs7574865 Polymorphism and Rheumatoid Arthritis: Debate Unresolved.

Publications

Association Between <i>STAT4</i> rs7574865 Polymorphism and Rheumatoid Arthritis: Debate Unresolved.

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