Reduced Risk Of Rheumatoid Arthritis Research Articles

Association between flavonoid intake and rheumatoid arthritis among US adults

Basic research shows that flavonoids have anti-inflammatory effects that influence rheumatoid arthritis (RA) in rats. Investigating potential dietary interventions for RA helps prevent the onset and progression of the disease. Clinical evidence on the association of flavonoid and subclass intake with RA is lacking. Using three survey cycles of 2007–2008, 2009–2010, and 2017–2018 from the National Health and Nutrition Survey and the United States Department of Agriculture's Food and Nutrient Database for Dietary Studies (FNDDS), we analyzed 7,419 American adults (≥20 years old). The values of flavonoid and subclass intake were calculated using FNDDS. The status questions for self-reported RA were from the NHANES codebook. Weighted analyses, revealed that among the 7,419 participants included in this study (mean age of 44.69 years [standard error, 0.40] and 3,584 [48.31%] were female), 408 met the classification criteria for RA. According to the multivariable logistic regression model, compared with the risk of RA in the first quartile (Q1), the risks of RA in the second quartile (Q2), the third quartile (Q3) and the fourth quartile (Q4) were lower (Q2: OR=0.55, 95% CI: 0.38–0.80; Q3: OR=0.66, 95% CI: 0.44–0.97; Q4: OR=0.64, 95% CI: 0.46–0.89; trend: P=.03). The association between total flavonoids and RA remained significant after full consideration of confounding factors. With regard to the subclasses of flavonoids, high flavanones intake was associated with low RA prevalence in Model 3 (Q3: OR= 0.60, 95% CI:0.39–0.92; Q4: OR = 0.56, 95% CI: 0.32–0.99, trend: P=.02), but no such association was found in the other subclasses. Total flavonoids intake protected against RA, and the risk of developing RA decreased significantly with increasing intake of total flavonoids. Total flavonoids and flavanones were significantly associated with reduced RA risk for the American adult population. We highlighted the importance of employing diverse methodologies to assess the health effects of flavonoids.

Assessment of interleukin 6 gene polymorphisms with rheumatoid arthritis.

Rheumatoid arthritis (RA) is complex autoimmune system disease and significant impact on the health of population in our world. Numerous studies confirmed that genetic factors play a crucial role in the pathogenesis of RA. In this current study, we aimed to investigate IL-6 polymorphisms and RA risk in Chinese Han population. 508 RA patients and 494 age- and gender- matched healthy controls were recruited, all subjects were genotyped with an Agena MassARRAY platform. Subsequently, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression after adjusting for age and gender. Our results suggested that IL-6 rs2243289 allele and genotype frequencies were associated with reduced RA risk under all genetic models (all p<0.05). Stratification analysis revealed that IL-6 rs2243289 polymorphism was significant associated with decreased the risk of RA in the old groups (age>54) (all p<0.05). However, IL-6 rs2069837 and rs1800796 polymorphisms were associated with increased risk of RA among the young groups (age≤54) (all p<0.05). In addition, subgroup analysis by gender suggested that IL-6 rs2069837 and rs1800796 polymorphism were interacted with increased the risk of RA in males (all p<0.05). Besides, IL-6 rs2243289 was associated with reduced RA risk in females. In conclusion, our results demonstrated the correlation between IL and 6 polymorphisms and RA susceptibility and confirmed for the first time that the relationship was restricted to age and gender in Chinese Han population.

Genetic analysis of the relation between IL2RA/IL2RB and rheumatoid arthritis risk

BackgroundThe biological mechanisms driving disease chronicity in rheumatoid arthritis (RA) are largely unidentified. Therefore, we aimed to determine genetic risk factors for RA.MethodsIn this case–control study, which includes samples from 499 patients and 507 healthy controls, six single‐nucleotide polymorphisms (SNPs) in interleukin‐2 receptor subunit alpha (IL2RA) and IL2RB were selected. Genotyping was performed using the Agena MassARRAY platform, and the statistical analyses were performed using the chi‐squared and Fisher's exact tests, genetic model analysis, and haplotype analysis.ResultIn the allele model, using the chi‐squared test, the result showed that rs791588 in IL2RA was associated with a decreased RA risk (odds ratios [OR] = 0.74, 95% confidence intervals [CI] = 0.62–0.89, p = 0.0014) after adjusting for age and gender. In the genetic model, logistic regression analyses revealed that rs791588 was associated with a decreased risk of RA under the codominant model, dominant model, recessive model, and log‐additive model. Stratification analysis revealed that two SNPs (rs791588 and rs2281089) were significantly associated with a reduced RA risk in an allele and genetic model after stratification by gender or age (p < 0.05). In addition, the haplotypes “Crs12569923Grs791588” and “Crs12569923Trs791588” of IL2RA was associated with an increased risk of RA adjusted by age and gender (OR = 1.35, 95% CI: 1.12–1.64, p = 0.0016; OR = 1.24, 95% CI: 1.03–1.48, p = 0.021).ConclusionThis finding indicates that the inherited altered genetic constitution at IL2RA may predispose to a less destructive course of RA.

Long-term dietary quality and risk of developing rheumatoid arthritis in women

ObjectivesTo evaluate the association between long-term dietary quality, measured by the 2010 Alternative Healthy Eating Index, and risk of rheumatoid arthritis (RA) in women.MethodsWe prospectively followed 76 597 women in...

CYB5A polymorphism increases androgens and reduces risk of rheumatoid arthritis in women.

IntroductionRheumatoid arthritis (RA) is characterized by decreased androgen levels, which was the first hormonal abnormality described. Several studies indicated that steroidogenesis is directed towards endogenous glucocorticoids at the expense of androgens. The decisive step governing androgen synthesis is the 17,20-lyase activity of the CYP17A1 gene-encoded enzyme cytochrome P450 17A1. Here, we focused on the role in RA of the critical cofactor for 17,20-lyase activity, cytochrome b5, encoded by the CYB5A gene.MethodsData sets of two genome wide RA association studies (GWAS) were screened for single nucleotide polymorphisms (SNP) in the CYB5A gene. Candidate SNPs in CYB5A were studied in a case–control study population of Slovakia. Expression analyses were done in synovial fibroblasts from RA patients by quantitative real-time polymerase chain reaction, and cytochrome b5–expression was detected by immunohistochemistry. Real-life androgen production after steroid conversion was measured using radiolabeled substrates.ResultsThe study identified the RA-associated intronic SNP rs1790834 in the CYB5A gene in one GWAS and confirmed the same SNP in our study. The minor allele reduced RA risk selectively in women (P = 4.1*10−3; OR = 0.63, 95% CI [0.46-0.86]). The protective effect was confined to rheumatoid factor-positive (OR = 0.53, [0.37-0.75]) and anti-cyclic citrullinated peptide-positive (OR = 0.58, [0.41-0.83]) cases, respectively. The protective allele doubles CYB5A mRNA-expression resulting in 2-3fold activation of steroid 17,20-lyase activity, and protective allele was accompanied by a higher density of cytochrome b5-positive cells in synovial tissue.ConclusionsCYB5A is the first RA susceptibility gene involved in androgen synthesis. Our functional analysis of SNP rs1790834 indicates that it contributes to the sex bias observed in RA.

Parity and HLA alleles in risk of rheumatoid arthritis.

Specific HLA II alleles are associated with rheumatoid arthritis (RA) risk and others with protection. Risk-associated alleles encode similar amino acid sequences from 70 through 74 of HLA-DRβ1 (QKRAA, QRRAA, RRRAA), referred to as the "shared epitope" (SE) and protective alleles encode DERAA at the same location. Fetal-maternal cell exchange results in long-term microchimerism i.e. harboring small numbers of genetically disparate cells. Women with RA who lack the SE were recently found to harbor microchimerism with the SE more often than healthy women. This finding raises the question whether microchimerism with DERAA confers benefit against RA and is underscored by the observation that overall parity reduces RA risk. While there is currently no test for microchimerism with DERAA, we conducted studies to ask whether parity benefits women at risk for RA, either because they have the SE or lack the protective DERAA sequence. HLA genotyping was conducted for 310 RA and 571 healthy women. Parity was associated with reduced RA risk in women aged <45 years (RR 0.53, 95% CI 0.34-0.82) and further analyses examined this group. RA risk reduction with parity was greater among women with the SE than SE-negative women (RR 0.42, 95%CI 0.22-0.79 vs. RR 0.79, 0.38-1.64). Among women without DERAA, RA risk was significantly reduced with parity (RR 0.44, 95% CI 0.26-0.74) but not among DERAA-positive women (RR 0.95 95% CI 0.34-2.65). In summary, results indicate the effect of parity varied according to a woman's HLA-genotype, and women at increased risk of RA benefited most.

Parity and HLA alleles in risk of rheumatoid arthritis

Specific HLA II alleles are associated with rheumatoid arthritis (RA) risk and others with protection. Risk-associated alleles encode similar amino acid sequences from 70 through 74 of HLA-DRβ1 (QKRAA, QRRAA, RRRAA), referred to as the “shared epitope” (SE) and protective alleles encode DERAA at the same location. Fetal-maternal cell exchange results in long-term microchimerism i.e. harboring small numbers of genetically disparate cells. Women with RA who lack the SE were recently found to harbor microchimerism with the SE more often than healthy women. This finding raises the question whether microchimerism with DERAA confers benefit against RA and is underscored by the observation that overall parity reduces RA risk. While there is currently no test for microchimerism with DERAA, we conducted studies to ask whether parity benefits women at risk for RA, either because they have the SE or lack the protective DERAA sequence. HLA genotyping was conducted for 310 RA and 571 healthy women. Parity was associated with reduced RA risk in women aged &lt;45 years (RR 0.53, 95% CI 0.34-0.82) and further analyses examined this group. RA risk reduction with parity was greater among women with the SE than SE-negative women (RR 0.42, 95%CI 0.22-0.79 vs. RR 0.79, 0.38-1.64). Among women without DERAA, RA risk was significantly reduced with parity (RR 0.44, 95% CI 0.26-0.74) but not among DERAA-positive women (RR 0.95 95%CI 0.34-2.65). In summary, results indicate the effect of parity varied according to a woman’s HLA-genotype, and women at increased risk of RA benefited most.