Home About us Contact
|
Home About us Contact | ||
|
|
||
Rheumatoid Arthritis Susceptibility (rheumatoid + arthritis_susceptibility)
Selected AbstractsAssociation of vitamin D receptor genotypes with early onset rheumatoid arthritisINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 1 2001J. R. Garcia-Lozano The presence of certain vitamin D receptor (VDR) genotypes has been associated with low bone mineral density (BMD) in elderly populations as well as with accelerated bone loss in patients with rheumatoid arthritis (RA). In the present study, VDR genotypes from 120 Spanish patients with RA were investigated. Three VDR gene polymorphisms (BsmI, ApaI and TaqI) were investigated using polymerase chain reaction followed by enzymatic digestion. The distributions of VDR allelic frequencies were similar in patients and controls and therefore no influence of VDR polymorphisms on rheumatoid arthritis susceptibility could be demonstrated. However, in an analysis of the clinical features of the different VDR-related genetic subgroups, the BB/tt genotype, defined by the BsmI and TaqI restriction site polymorphisms, was identified to be weakly associated with an early onset RA in female patients. This VDR genotype has been associated with a low BMD level in various studies. When patients were stratified according to the presence of the shared HLA epitope SE, it was found that SE + female patients bearing the BB/tt genotype showed the earliest disease onset. The mechanisms by which the VDR polymorphism is associated with RA is unknown, but they could be related to the immunoregulatory properties of vitamin D. [source] Smoking increases rheumatoid arthritis susceptibility in individuals carrying the HLA,DRB1 shared epitope, regardless of rheumatoid factor or anti,cyclic citrullinated peptide antibody statusARTHRITIS & RHEUMATISM, Issue 2 2010So-Young Bang Objective Smoking is associated with rheumatoid arthritis (RA) in individuals with the HLA,DRB1 shared epitope (SE). SE alleles have been shown to be predominantly associated with anti,cyclic citrullinated peptide (anti-CCP),positive RA. These risk factors have not been identified for anti-CCP,negative RA. The aim of this study was to investigate whether SE-containing HLA,DRB1 alleles, smoking, or the combination of these factors contributes to the development of RA, depending on the presence or absence of serologic markers, in a Korean population. Methods All of the patients with RA (n =1,482) and all of the control subjects (n = 1,119) were Korean. Four-digit HLA,DRB1 typing was performed by a conventional polymerase chain reaction,sequence-based typing method. Information about smoking history was obtained through a questionnaire. The patients with RA were tested for anti-CCP antibodies and rheumatoid factor (RF). Results The SE alleles had significant effects on anti-CCP antibody and RF formation. The DRB1*0901 allele was associated with the presence of anti-CCP antibodies (odds ratio [OR] 2.49) and RF (OR 2.09). SE alleles and smoking were associated with both anti-CCP,positive and anti-CCP,negative RA. The combination of smoking and double copies of the SE allele increased the risk of anti-CCP,positive RA 36.11-fold and increased the risk of anti-CCP,negative RA 12.29-fold, compared with the risk among nonsmokers not carrying SE alleles. Interactions between SE alleles and smoking were observed for both anti-CCP,positive and RF-positive RA, although the associations of RF-positive RA could be consequences of the underlying anti-CCP antibody status. Conclusion We demonstrated that the combination of SE alleles and smoking is associated with RA susceptibility regardless of anti-CCP antibody or RF status, but that the combination shows stronger effects in anti-CCP,positive/RF-positive patients with RA than in anti-CCP,negative/RF-negative patients with RA. The SE,smoking interactions were present in anti-CCP,positive and RF-positive RA. [source] TRAF1 polymorphisms associated with rheumatoid arthritis susceptibility in Asians and in CaucasiansARTHRITIS & RHEUMATISM, Issue 9 2009Tae-Un Han Objective Recent genome-wide association scans and replication studies of European populations have disclosed several single-nucleotide polymorphisms (SNPs) associated with rheumatoid arthritis (RA) susceptibility. The aim of this study was to evaluate the RA-associated loci by genotyping previously reported SNPs and additional tag SNPs in a Korean population. Methods A total of 1,316 unrelated RA patients and 1,006 controls were genotyped for 12 SNPs identified in genome-wide scans and for 12 additional tag SNPs in IL2RB, OLIG3,TNFAIP3, PTPN22, and TRAF1,C5, and the findings were statistically compared. Results None of the SNPs tested was associated with RA susceptibility, except rs7021206 in TRAF1 intron 3 (P = 0.0032) and, among the SNPs previously reported, rs6457617 in HLA (P = 4.6 × 10,35). The association of rs7021206 was positive in patients who were seropositive for rheumatoid factor (P = 0.0051) or for anti,cyclic citrullinated peptide autoantibodies (P = 0.0062). However, Korean patients were negative for the association of rs3761847 in the TRAF1,C5 intergenic region previously reported in Caucasians. Linkage disequilibrium between rs3761847 and rs7021206 was not as high in Koreans (r2 = 0.37) as in Caucasians (r2 = 0.67), which explains the lack of association of rs3761847 in Koreans. Accordingly, RA susceptibility was localized to an extended haplotype marked by rs7021206 rather than rs3761847, and SNPs highly correlated with rs7021206 (r2 , 0.81) extended from rs1953126 in the PHF19,TRAF1 intergenic region to rs2900180 in the TRAF1,C5 intergenic region, spanning 66 kb. Conclusion Our results demonstrate that within and around TRAF1, excluding PHF19 and C5, SNPs highly correlated with rs7021206, but not those correlated with rs3761847, are associated with RA in both Asians and Caucasians and are possibly correlated with causative variations. [source] The PRL ,1149 G/T polymorphism and rheumatoid arthritis susceptibilityARTHRITIS & RHEUMATISM, Issue 5 2009Yvonne C. Lee Objective Previous studies have demonstrated that the PRL ,1149 T (minor) allele decreases prolactin expression and may be associated with autoimmune disease. The aim of this study was to determine the role of the PRL ,1149 G/T polymorphism (rs1341239) in rheumatoid arthritis (RA) susceptibility. Methods We examined the association between PRL ,1149 G/T and RA risk in 4 separate study populations, consisting of a total of 3,405 RA cases and 4,111 controls of self-reported white European ancestry. Samples were genotyped using 1 of 3 genotyping platforms, and strict quality control metrics were applied. We tested for association using a 2-tailed Cochran-Mantel-Haenszel additive, fixed-effects model. Results In the individual populations, odds ratios (ORs) for an association between PRL ,1149 T and RA risk ranged from 0.80 to 0.97. In a joint meta-analysis across all 4 populations, the OR for an association between PRL ,1149 T and RA risk was 0.90 (95% confidence interval 0.84,0.96, P = 0.001). Conclusion Our findings indicate a possible association between the PRL ,1149 T allele and decreased RA risk. The effect size is small but similar to ORs for other genetic polymorphisms associated with complex traits, including RA. [source] Genome-wide association study of rheumatoid arthritis in the Spanish population: KLF12 as a risk locus for rheumatoid arthritis susceptibilityARTHRITIS & RHEUMATISM, Issue 8 2008Antonio Julią Objective To identify new genes associated with susceptibility to rheumatoid arthritis (RA), using a 2-stage genome-wide association study. Methods Following a liability-based study design, we analyzed 317,503 single-nucleotide polymorphisms (SNPs) in 400 patients with RA and 400 control subjects. We selected a group of candidate SNPs for replication in an independent group of 410 patients with RA and 394 control subjects. Using data from the 3 previous genome-wide association studies in RA, we also looked for genomic regions showing evidence of common association signals. Finally, we analyzed the presence of genome-wide epistasis using the binary test implemented in the PLINK program. Results We identified several genomic regions showing evidence of genome-wide association (P < 1 × 10 ,5). In the replication analysis, we identified KLF12 SNP rs1324913 as the most strongly associated SNP (P = 0.01). In our study, we observed that this SNP showed higher significance than PTPN22 SNP rs2476601, in both the genome-wide association studies and the replication analyses. Furthermore, the integration of our data with those from previous genome-wide association studies showed that KLF12 and PTPRT are the unique loci that are commonly associated in 3 different studies (P = 0.004 and P = 0.002 for KLF12 in the Wellcome Trust Case Control Consortium study and the Brigham and Women's Rheumatoid Arthritis Sequential Study genome-wide association study, respectively). The genome-wide epistasis analysis identified several SNP pairs close to significance after multiple test correction. Conclusion The present genome-wide association study identified KLF12 as a new susceptibility gene for RA. The joint analysis of our results and those from previous genome-wide association studies showed genomic regions with a higher probability of being genuine susceptibility loci for RA. [source] | ||||||||||