Most Common Single-Nucleotide Polymorphisms Associated With Rheumatoid Arthritis in Persons of European Ancestry Confer Risk of Rheumatoid Arthritis in African Americans

University of Alabama at Birmingham, 1530 3rd Avenue South, SHEL 210, Birmingham, AL 35294-2182, USA.
Arthritis & Rheumatology (Impact Factor: 7.76). 12/2010; 62(12):3547-53. DOI: 10.1002/art.27732
Source: PubMed


Large-scale genetic association studies have identified >20 rheumatoid arthritis (RA) risk alleles among individuals of European ancestry. The influence of these risk alleles has not been comprehensively studied in African Americans. We therefore sought to examine whether these validated RA risk alleles are associated with RA risk in an African American population.
Twenty-seven candidate single-nucleotide polymorphisms (SNPs) were genotyped in 556 autoantibody-positive African Americans with RA and 791 healthy African American control subjects. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for each SNP were compared with previously published ORs for RA patients of European ancestry. We then calculated a composite genetic risk score (GRS) for each individual based on the sum of all risk alleles.
Overlap of the ORs and 95% CIs between the European and African American populations was observed for 24 of the 27 candidate SNPs. Conversely, 3 of the 27 SNPs (CCR6 rs3093023, TAGAP rs394581, and TNFAIP3 rs6920220) demonstrated ORs in the opposite direction from those reported for RA patients of European ancestry. The GRS analysis indicated a small but highly significant probability that African American patients relative to control subjects were enriched for the risk alleles validated in European RA patients (P = 0.00005).
The majority of RA risk alleles previously validated for RA patients of European ancestry showed similar ORs in our population of African Americans with RA. Furthermore, the aggregate GRS supports the hypothesis that these SNPs are risk alleles for RA in the African American population. Future large-scale genetic studies are needed to validate these risk alleles and identify novel RA risk alleles in African Americans.

Download full-text


Available from: Leigh Callahan,
26 Reads
  • Source
    • "These findings were found in studies performed by the WTCCC [106] and Korman et al. [84] respectively . The study, conducted by Hughes et al. [86], was not in line with the study of Stahl et al. [85] for the association of CCR6 and TNFAIP3 with RA in African Americans and Europeans respectively. Table 2, summarizing the above findings, showed the studies that confirm/contradict one another in the association of certain genes with RA in different ethnicities. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Genetics of autoimmune diseases represent a growing domain with surpassing biomarker results with rapid progress. The exact cause of Rheumatoid Arthritis (RA) is unknown, but it is thought to have both a genetic and an environmental bases. Genetic biomarkers are capable of changing the supervision of RA by allowing not only the detection of susceptible individuals, but also early diagnosis, evaluation of disease severity, selection of therapy, and monitoring of response to therapy. This paper is concerned with not only the genetic biomarkers of RA but also the methods of identifying them. Many of the identified genetic biomarkers of RA were identified in populations of European and Asian ancestries. The study of additional human populations may yield novel results. Most of the researchers in the field of identifying RA biomarkers use single nucleotide polymorphisms (SNPs) approaches to express the significance of their results. Although, haplotype blocks methods are expected to play a complementary role in the future of that field.
    Journal of Advanced Research 02/2015; DOI:10.1016/j.jare.2015.01.008
  • Source
    • "An association between F127C and A125V human polymorphism in TNFAIP3 and autoimmunity in African Americans was reported by Lodolce JP. et al. [14]. The majority of RA risk alleles previously validated for RA patients of European ancestry showed similar ORs in the population of African Americans with RA [15]. Studies which tested the 6q23 region in Tunisian population revealed a trend of an association of rs6920220-A allele with RA and genotypes containing this allele were in a higher proportion in RA patients than in matched controls [16]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic destructive inflammation in synovial joints. It is well known that genetic and environmental risk factors and their interaction contribute to RA pathogenesis. This study aimed to investigate the association between the critical polymorphisms in the tumor necrosis factor α (TNFα)-induced protein 3(TNFAIP3) gene and the risk of RA in a large northern Chinese Han population. Methods A case–control study of 1280 RA patients and 1280 matched healthy controls was conducted. Results This study showed that carriers of the rs2230926 TG genotype or rs10499194 CT genotype had an increased risk for RA compared with those carrying the wild genotype (rs2230926: OR = 1.48, 95% CI = 1.17-1.86, p = 0.001; rs10499194: OR = 2.00, 95% CI = 1.46-2.74, p < 0.001). The combined rs2230926TG/GG or rs10499194 CT/TT were associated with an increased risk of RA (ORs were 1.50 and 2.01, 95% CIs were 1.19-1.88 and 1.47-2.74, respectively, both p < 0.001). There was not significant association between rs13207033 polymorphism and RA risk. Subset analysis stratified to gender showed that the increased risks were significant among the genotypes TG, TG/GG of rs2230926 and CT, CT/TT of rs10499194 and the corresponding ORs were 1.42 (95% CI = 1.10-1.83, p = 0.006), 1.44(95% CI = 1.12-1.85, p = 0.004), 1.52(95% CI = 1.05-2.20, p = 0.026) and 1.52(95% CI = 1.06-2.19, p = 0.023) in the female population. Stratified analyses by age found that rs2230926(TG, TG/GG) and rs10499194(CT, CT/TT) polymorphisms were associated with RA risks in population ≤53 years old and among >53 years old only rs10499194(CT, TT, CT/TT) polymorphism had significant results. The interaction analysis suggested that individuals with both risk genotypes of the two SNPs have a higher elevated risk of RA than those with only one of them (ORs were 3.44 compared to 1.74 and 1.35). The haplotype results showed that individuals with the rs2230926G-rs13207033G-rs10499194C haplotype were associated with increased risks of RA (OR = 1.37, 95% CI = 1.08-1.74, p = 0.010). Conclusions Rs10499194 and rs2230926 polymorphisms in the TNFAIP3 gene region may be susceptibility factors for rheumatoid arthritis in the northern Chinese Han population.
    BMC Medical Genetics 05/2014; 15(1):56. DOI:10.1186/1471-2350-15-56 · 2.08 Impact Factor
  • Source
    • "ROS-induced cartilage destruction can be inhibited by endogenous SOD or GSH. Imbalance in this mechanism during an aggravated cellular response in arthritis promotes the ROS-induced destruction of bone and cartilage [57, 58]. Our data strongly support these studies in case of arthritic control animals since we have observed a significant rise in the levels of NO and PO with parallel decrease in GSH and SOD. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Rheumatoid arthritis (RA) is potentially devastating condition which lacks good treatment options. Pro-inflammatory cytokines interleukin-1beta (IL-1 β ), tumor necrosis factor-alpha (TNF- α ), and oxidative stress markers such as nitric oxide (NO) and peroxide (PO) are mediators of RA pathogenesis. In the present study N-[2,4,5-trihydroxy-6-(hydroxymethyl) tetrahydro-2H-pyran-3-yl]acrylamide (NHAG), analogue of glucosamine, was evaluated in adjuvant-induced arthritic model of rats. The disease progression was monitored by analysing arthritis scoring, loss of body weight, paw oedema, and histological changes in joints. RA associated hyperalgesia was evaluated by gait analysis. The serum or plasma levels of NO, PO, glutathione (GSH) superoxide dismutase (SOD) IL-1 β and TNF- α were analyzed to monitor the state of disease severity. The arthritic control animals exhibited significant increase in arthritic score (P < 0.003) and paw oedema (P < 0.001) with parallel loss in body weight (P < 0.04). The NHAG-treated arthritic animals exhibited refinement in the gait changes associated with arthritis. NHAG also significantly decreased the NO (P < 0.02) and PO (P < 0.03) with concurrent increased in GSH (P < 0.04) and SOD (P < 0.007). Both IL-1 β (P < 0.001) and TNF- α (P < 0.001), were significantly decreased in NHAG-treated group. Thus NHAG might have a therapeutic potential for arthritis by exerting antioxidative and immunomodulatory effects.
    07/2013; 2013:487610. DOI:10.1155/2013/487610
Show more