Correction: Association of the FCRL3 gene with rheumatoid arthritis: a further example of population specificity?
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ABSTRACT:
SUBMITTER: Eyre S
PROVIDER: S-EPMC2575637 | biostudies-literature | 2008 Jan
REPOSITORIES: biostudies-literature
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Project description:Association of a functional promoter polymorphism mapping to the Fc receptor-like 3 (FCRL3) gene has recently been reported and replicated with rheumatoid arthritis (RA) in Japanese populations. The aim of this study was to investigate association of the FCRL3 gene with RA in UK subjects. DNA was available from 1065 patients with RA and 2073 population controls from the UK. Four single nucleotide polymorphism (SNP) markers (FCRL3-169*C/T (fclr3_3, rs7528684), fclr3_4 (rs11264799), fclr3_5 (rs945635), fclr3_6 (rs3761959)) all previously associated with RA in a Japanese population were genotyped in 761 RA samples and 484 controls. In the remaining samples, only the putative disease causal polymorphism, FCRL3-169*C/T, was tested. Genotyping was performed using either the Sequenom MassArray iPlex platform or a 5' Allelic discrimination assay (Taqman, ABI). Extensive linkage disequilibrium was present across the promoter SNPs genotyped (r2 values = 0.60-0.98). Allele frequencies did not differ between RA cases and controls either for the putative disease causal polymorphism (odds ratio FCRL3-169*C allele = 0.97 (0.87-1.07), p = 0.51) or for the other SNPs tested. Similarly, no association was detected with RA using haplotype analysis or when stratification by shared epitope carriage or by presence of rheumatoid factor was undertaken. This study was powered to detect an effect size of 1.24 or greater for the FCRL3-169*C/T functional promoter polymorphism but no evidence for association was detected, suggesting that this gene will not have a substantial effect in determining susceptibility to RA in populations of Northern European descent.
| S-EPMC1779391 | biostudies-literature
Project description:BackgroundAn association between susceptibility to rheumatoid arthritis and the Fc receptor-like 3 gene (FCRL3) has been reported in a Japanese population. A case-control study showed that the strongest evidence of the association was derived from a polymorphism in the promoter region of FCRL3, which has a regulatory effect on the expression of the gene.ObjectiveTo validate the findings of this previous report by examining the -169C-->T single nucleotide polymorphism (SNP) in a large cohort.Methods752 unrelated cases and 940 controls were genotyped. All the samples were from the same ethnic background as the original study. Genotyping was done using 5' allelic discrimination assays. Association between susceptibility to rheumatoid arthritis and -169C-->T SNP was examined by chi(2) testing.ResultsAs in the previous study, the SNP showed significant differences between cases and controls (p = 0.022, odds ratio = 1.18, 95% confidence interval 1.02 to 1.35).ConclusionsThis result supports a genetic association of the FCRL3 promoter polymorphism with rheumatoid arthritis.
| S-EPMC1798145 | biostudies-literature
Project description:BackgroundA Japanese study has described a strong association between rheumatoid arthritis and several polymorphisms located in the Fc receptor-like 3 (FCRL3) gene, a member of a family of genes related to Fc receptors located on chromosome 1q21-23.ObjectivesTo evaluate the association between rheumatoid arthritis and FCLR3 polymorphisms in a large cohort of Caucasian patients with rheumatoid arthritis and healthy controls of Spanish origin. Owing to the described functional link between the FCRL3 polymorphisms and the transcription factor nuclear factor kappaB (NFkappaB), a functional polymorphism located in the NFkappaB1 gene was included.Methods734 patients with rheumatoid arthritis from Madrid and Granada, Spain, were included in the study, along with 736 healthy controls. Polymorphisms in the FCRL3 gene were studied by TaqMan technology. The -94ins/delATTG NFkappaB1 promoter polymorphism was analysed by fragment analysis after polymerase chain reaction with labelled primers. Genotypes were compared using 3x2 contingency tables and chi2 values.ResultsNo overall differences were found in any of the FCRL3 polymorphisms and in the NFkappaB1 promoter polymorphism when patients were compared with controls. However, when stratified according to NFkappaB1 genotypes, a susceptibility effect of FCRL3 polymorphisms was observed in patients who were heterozygotes for NFkappaB1 (pc = 0.003).ConclusionsThe FCRL3 polymorphisms associated with rheumatoid arthritis in a Japanese population are not associated per se with rheumatoid arthritis in a Spanish population. A genetic interaction was found between NFkappaB1 and FCRL3 in Spanish patients with rheumatoid arthritis. These findings may provide a general rationale for divergent genetic association results in different populations.
| S-EPMC1798300 | biostudies-literature
Project description:Background and Objectives: Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune, multi-factorial disease, in which environmental and genetic factors play a major role. RA is possibly linked to vitamin D deficiency and vitamin D receptor (VDR) gene polymorphisms, and research demonstrates that FokI variant susceptibility is associated with increased disease risk among Caucasians. The aim of this study was to evaluate vitamin D deficiency prevalence and its correlation to RA clinical parameters, and to determine the possible association of VDR gene polymorphisms and RA susceptibility in the Lithuanian population. Materials and Methods: Overall, 206 RA patients and 180 age- and sex-matched healthy controls were enrolled at Vilnius University Hospital Santaros Klinikos after informed consent was obtained. The disease activity score 28 C-reactive protein (DAS28 CRP), rheumatoid arthritis impact of disease (RAID) score, and health assessment questionnaire (HAQ) were recorded in RA patients, and 25(OH)D serum levels were evaluated by chemiluminescent microparticle immunoassay for all subjects. Four VDR gene polymorphisms, BsmI, FokI, ApaI, and TaqI, were assessed using real-time PCR instruments and genotyping assays in both groups. Results: The study registered a high prevalence of 25(OH)D deficiency (<50 nmol/L) in RA patients (61.55% (n = 127)). The mean serum concentration in RA patients (44.96 ± 21.92 (nmol/L)) was significantly lower than in the healthy controls (54.90 ± 22.82 (nmol/L)), p < 0.0001. A significant inverse correlation between vitamin D level, DAS28 CRP, and HAQ scores was confirmed in RA patients, with p < 0.05. Still, there was no significant association between the overall risk of RA disease for any allele or genotype of the four VDR loci tested. Conclusions: The study confirmed that vitamin D deficiency is prevalent among RA patients and the 25(OH)D level is significantly lower compared with healthy controls. Lower vitamin D concentration was related with increased disease activity and disability scores. However, genetic analysis of four VDR polymorphisms did not confer the susceptibility to RA in Lithuanian population.
| S-EPMC8065838 | biostudies-literature
Project description:ObjectiveRA patients have an increased risk of cardiovascular (CV) disease, although the mechanisms are unclear. As RA and CV disease may be associated through lipid profiles, we examined whether single nucleotide polymorphisms (SNPs) associated with RA susceptibility were associated with low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglyceride (TG) levels in RA subjects.MethodsPatients (n = 763) enrolled in the Veterans Affairs RA registry who were not on hydroxymethylglutaryl-CoA reductase inhibitor were genotyped for human leukocyte antigen shared epitope (HLA-DRB1-SE) and SNPs in the following genes: CTLA-4 (cytotoxic T-lymphocyte antigen 4), IL-10, PTPN22 (protein tyrosine phosphatase, non-receptor type 22), REL (c-Rel), STAT4 (signal transducer and activator of transcription protein), TNF- and TRAF1 (TNF receptor-associated factor 1). Other covariates included patient characteristics (age, gender, race, smoking status, education, BMI, modified CharlsonDeyo comorbidity index), CV characteristics (hypertension, diabetes, alcohol abuse), pharmacologic exposures (MTX, anti-TNF, glucocorticoids) and RA severity/activity markers (RA disease duration, mean DAS, CRP, RF positivity, anti-CCP positivity). Multivariate linear regression was performed to determine the factors associated with LDL, HDL and TG levels.ResultsThe REL SNP rs9309331 homozygous minor allele was associated with higher LDL levels. Caucasian race and increasing BMI were associated with lower HDL. Factors associated with higher TG were diabetes, Caucasian race and higher BMI.ConclusionThe REL SNP rs9309331 was associated with LDL levels in our study. This association is a possible explanation of the increased risk of RA patients for CV disease and requires further inquiry.
| S-EPMC4023559 | biostudies-literature
Project description:BackgroundRecently, increasing studies have revealed that leptin is involved in the development of rheumatoid arthritis (RA). This study is aimed at exploring the association of leptin gene single nucleotide polymorphisms (SNPs) with susceptibility to RA in a Chinese population.MethodsWe recruited 600 RA patients and 600 healthy controls from a Chinese population and analyzed their three leptin SNPs (rs10244329, rs2071045, and rs2167270) using the improved Multiplex Ligase Detection Reaction (iMLDR) assays. The associations of these SNPs with clinical manifestations of RA were also analyzed. Enzyme-linked immunosorbent assay (ELISA) was performed for plasma leptin determination.ResultsNo significant difference in either allele or genotype frequencies of these three SNPs between RA patients and healthy controls was observed (all P > 0.05). Association between the genotype effects of dominant, recessive models was also not found (all P > 0.05). No significant difference in plasma leptin levels was detected between RA patients and controls (P > 0.05).ConclusionLeptin gene (rs10244329, rs2071045, and rs2167270) polymorphisms are not associated with RA genetic susceptibility and its clinical features in the Chinese population.
| S-EPMC7559230 | biostudies-literature
Project description:BackgroundHuman leucocyte antigen is the only genetic risk factor for rheumatoid arthritis (RA) that has been consistently observed in different populations. A number of other genes such as PTPN22 and PADI4 showed population-specific association with RA susceptibility. Recently, Fc receptor-like 3 (FCRL3) gene was found to be associated with RA susceptibility in Japanese, but with conflicting results in other populations.ObjectiveTo investigate the association of FCRL3 polymorphism with RA susceptibility and severity in Dutch Caucasian patients with RA, as well as to perform a meta-analysis to reveal the contribution of this gene to RA susceptibility.MethodsA total of 931 Dutch RA cases and 570 unrelated Dutch controls were genotyped for four FCRL3 single-nucleotide polymorphisms (SNPs). Genotyping was performed using the MassArray matrix-assisted laser desorption ionisation-time-of-flight mass spectrometry. Association of the FCRL3 SNPs with susceptibility to RA was examined by single-marker, carrier and haplotype analysis.ResultsCarrier analysis of the SNP (rs7528684) revealed the association of CC genotype with a higher risk of developing RA as compared with TT and TC carriers (p = 0.039 and OR = 1.31). There was no significant difference in the genotype and allele frequencies of all investigated SNPs between cases and controls. Meta-analysis of all studies comparing 9467 individuals showed that the OR for the CC genotype to develop RA was 1.2 and the p value <0.001.ConclusionA promoter polymorphism of FCRL3 (rs7528684) is associated with an increased risk of developing RA in Dutch Caucasians, suggesting that this association is relevant for RA in both Japanese and Caucasian populations.
| S-EPMC1954681 | biostudies-literature
Project description:BackgroundRecent evidences have revealed that resistin is associated with the development of rheumatoid arthritis (RA). The aim of this study was to analyze the association of resistin gene single nucleotide polymorphisms (SNPs) with RA susceptibility.MethodsIn this study, we finally analyzed three resistin SNPs (rs1862513, rs3745368, and rs3745367) in 278 RA patients and 276 normal controls recruited from Chinese population using TaqMan SNP genotyping assays.ResultsThere were no significant differences for the distribution of allele and genotype frequencies of these three SNPs between RA patients and normal controls (all P > .05). The genotype effects of dominant, recessive models were also analyzed, and no significant association was detected (all P > .05). Haplotype analysis suggested that the frequency of haplotype GAA was notably lower in RA patients in comparison with normal controls (OR = 0.317, 95% CI: 0.125-0.807, P = .011).ConclusionIn a ward, our results indicated that resistin gene polymorphisms might affect the genetic predisposition of RA in Chinese population.
| S-EPMC6816980 | biostudies-literature
Project description:A recent study in the North American White population has documented the association of a common STAT4 haplotype (tagged by rs7574865) with risk for rheumatoid arthritis (RA) and systemic lupus erythematosus. To replicate this finding in the Korean population, we performed a case-control association study. We genotyped 67 single nucleotide polymorphisms (SNPs) within the STAT1 and STAT4 regions in 1123 Korean patients with RA and 1008 ethnicity-matched controls. The most significant four risk SNPs (rs11889341, rs7574865, rs8179673, and rs10181656 located within the third intron of STAT4) among 67 SNPs are identical with those in the North American study. All four SNPs have modest risk for RA susceptibility (odds ratio 1.21-1.27). A common haplotype defined by these markers (TTCG) carries significant risk for RA in Koreans [34 percent versus 28 percent, P=0.0027, OR (95 percent CI)=1.33 (1.10-1.60)]. By logistic regression analysis, this haplotype is an independent risk factor in addition to the classical shared epitope alleles at the HLA-DRB1 locus. There were no significant associations with age of disease onset, radiographic progression, or serologic status using either allelic or haplotypic analysis. Unlike several other risk genes for RA such as PTPN22, PADI4, and FCRL3, a haplotype of the STAT4 gene shows consistent association with RA susceptibility across Whites and Asians, suggesting that this risk haplotype predates the divergence of the major racial groups.
| S-EPMC2014726 | biostudies-literature
Project description:TBX21 (T-bet) is a member of the T-box family of transcriptional factors that contain a conserved DNA binding domain. TBX21 is a critical regulator of the commitment to the Th1 lineage and IFN-gamma production. Th1 and Th2 cells cross-regulate the differentiation of each other, and in this way TBX21 could be an attractive candidate gene for treating autoimmune disease such as rheumatoid arthritis (RA). In present study, we analyzed the genotypic frequencies of six polymorphisms of the TBX21 gene between the 367 RA patients and the 572 healthy controls. We showed that the g.-1514T>C and c.99C>G polymorphisms are suggestively associated with RA susceptibility. It is interesting that the genotypic frequencies of the TBX21 polymorphisms (g.-1514T>C and c.2103A>C) in the male RA patients were significantly different from the male control group (P=0.0016 and 0.045, respectively). We also found that the g.-1514T>C and c.2103A>C polymorphisms of the TBX21 gene in the male RA patients have significant association with the levels of anti-CCP (P=0.05) and rheumatoid factor (P=0.03), respectively. These results suggest that the polymorphisms of the TBX21 gene might be associated with the susceptibility to male RA patients.
| S-EPMC2679282 | biostudies-literature