OBJECTIVE: To investigate 1) tumor necrosis factor (TNF) microsatellite allele frequencies in rheumatoid arthritis (RA), and 2) associations between TNF microsatellites and RA-associated HLA specificities in order to build up extended HLA haplotypes. METHODS: Eighty-five caucasoid patients with RA and 109 healthy caucasoid controls were typed for TNF microsatellites a-d using fluorescent-labeled primers and semiautomated genotyping. A further 56 RA patients who were selected for having certain HLA-DRB1 types were also typed for these TNF microsatellites. Linkage disequilibria between TNF and HLA alleles were calculated, and extended haplotypes were established. RESULTS: The TNFa6 allele frequency was significantly increased in the RA patients compared with the controls (P = 0.0019, odds ratio [OR] 2.5, 95% confidence interval [95% CI] 1.3-4.6), an increase that was further evident in patients who were HLA-DRB1*0401 homozygous (P = 0.0003, OR 7.3, 95% CI 2.2-24.4). This increase was found to be due to association with HLA-DRB1*0401. No TNF microsatellite allele was found to be associated with HLA-DRB1*0404. Three HLA extended haplotypes were identified in the RA group: 1) HLA-DRB1*0401;TNFd4;TNFa6;TNFb5;HLA-B44; HLA-Cw5;HLA-A2, 2) HLA-DRB1*0301;TNFd2; TNFa2;TNFb3;HLA-B8;HLA-Cw7;HLA-A1, and 3) TNFd5;TNFc2;TNFa2;TNFb1;HLA-B62;HLA-Cw3. CONCLUSION: TNF microsatellites found to be associated with RA do not appear to be independent of class II HLA associations.
OBJECTIVE: To investigate 1) tumor necrosis factor (TNF) microsatellite allele frequencies in rheumatoid arthritis (RA), and 2) associations between TNF microsatellites and RA-associated HLA specificities in order to build up extended HLA haplotypes. METHODS: Eighty-five caucasoid patients with RA and 109 healthy caucasoid controls were typed for TNF microsatellites a-d using fluorescent-labeled primers and semiautomated genotyping. A further 56 RApatients who were selected for having certain HLA-DRB1 types were also typed for these TNF microsatellites. Linkage disequilibria between TNF and HLA alleles were calculated, and extended haplotypes were established. RESULTS: The TNFa6 allele frequency was significantly increased in the RApatients compared with the controls (P = 0.0019, odds ratio [OR] 2.5, 95% confidence interval [95% CI] 1.3-4.6), an increase that was further evident in patients who were HLA-DRB1*0401 homozygous (P = 0.0003, OR 7.3, 95% CI 2.2-24.4). This increase was found to be due to association with HLA-DRB1*0401. No TNF microsatellite allele was found to be associated with HLA-DRB1*0404. Three HLA extended haplotypes were identified in the RA group: 1) HLA-DRB1*0401;TNFd4;TNFa6;TNFb5;HLA-B44; HLA-Cw5;HLA-A2, 2) HLA-DRB1*0301;TNFd2; TNFa2;TNFb3;HLA-B8;HLA-Cw7;HLA-A1, and 3) TNFd5;TNFc2;TNFa2;TNFb1;HLA-B62;HLA-Cw3. CONCLUSION:TNF microsatellites found to be associated with RA do not appear to be independent of class II HLA associations.
Authors: Ning Wang; Nan Shen; Timothy J Vyse; Vidya Anand; Iva Gunnarson; Gunnar Sturfelt; Solbritt Rantapää-Dahlqvist; Kerstin Elvin; Lennart Truedsson; Bengt A Andersson; Charlotte Dahle; Eva Ortqvist; Peter K Gregersen; Timothy W Behrens; Lennart Hammarström Journal: Mol Med Date: 2011-08-04 Impact factor: 6.354
Authors: T Höhler; S Grossmann; B Stradmann-Bellinghausen; W Kaluza; E Reuss; K de Vlam; E Veys; E Märker-Hermann Journal: Ann Rheum Dis Date: 2002-03 Impact factor: 19.103