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GADD45a and GADD45b Genes in Rheumatoid Arthritis and Systemic Lupus Erythematosus Patients.

ABSTRACT: BACKGROUND:GADD45 genes are stress sensors in response to cellular stress response, activated signal pathways leading to the stimulation of inflammatory cytokines. This study is to examine the associations of GADD45a and GADD45b genes with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients. METHODS:230 patients of RA, 140 patients of SLE, and 191 healthy controls were enrolled. Genomic DNA was extracted from peripheral blood mononuclear cells and gene polymorphisms were genotyped by TaqMan assay. RNA expression was quantitated with real-time polymerase chain reaction. RESULTS:The RNA expression of the GADD45b gene was significantly lower in RA patients than the control cases (p = 0.03). The odds ratio of GADD45a genotype -589 CC (rs581000) was significantly low (OR = 0.36, 95% CI, 0.15-0.87) in DR4-negative RA patients. The odds ratio of GADD45b genotype -712CT (rs3795024) in DR4-negative RA patients was 0.41 (95% CI, 0.18-0.95). In clinical manifestation, the odds ratio of GADD45b -712CT genotype with anti-RNP antibody was 4.14 (95% CI, 1.10-15.63) in SLE patients. GADD45a genotype -589GG+GC was associated with rheumatoid factor (RF) in SLE patients. CONCLUSIONS:Genotypes GADD45a -589CC and GADD45b -712CT were shown to be less susceptible to RA and related to the disease state in SLE patients.

SUBMITTER: Li RN

PROVIDER: S-EPMC6617344 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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GADD45a and GADD45b Genes in Rheumatoid Arthritis and Systemic Lupus Erythematosus Patients.

Li Ruei-Nian RN Lin Yuan-Zhao YZ Pan Ya-Chun YC Lin Chia-Hui CH Tseng Chia-Chun CC Sung Wan-Yu WY Wu Cheng-Chin CC Ou Tsan-Teng TT Tsai Wen-Chan WC Yen Jeng-Hsien JH

Journal of clinical medicine 20190605 6

<h4>Background</h4>GADD45 genes are stress sensors in response to cellular stress response, activated signal pathways leading to the stimulation of inflammatory cytokines. This study is to examine the associations of GADD45a and GADD45b genes with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients.<h4>Methods</h4>230 patients of RA, 140 patients of SLE, and 191 healthy controls were enrolled. Genomic DNA was extracted from peripheral blood mononuclear cells and gene polymo ...[more]

PMID: 31195707

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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.

Dataset Information

GADD45a and GADD45b Genes in Rheumatoid Arthritis and Systemic Lupus Erythematosus Patients.

Publications

GADD45a and GADD45b Genes in Rheumatoid Arthritis and Systemic Lupus Erythematosus Patients.

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