Association of the CTLA4 3' untranslated region polymorphism with the susceptibility to rheumatoid arthritis.
Cytotoxic T-lymphocyte antigen 4 (CTLA4) gene polymorphism located in the 3' untranslated region (UTR) was investigated in 141 Spanish patients (38 men and 103 women) with rheumatoid arthritis (RA) and in 194 ethnically-matched healthy controls. Twenty alleles having different numbers of (AT) repeats (from 7 to 32) were found in this population. (AT)7 and (AT)16 were the most frequent alleles, and accounted for almost two-thirds of the allelic frequency in the control population. Consequently, alleles were assigned as L (large: 16 or more AT repeats) or S (short: less than 16 AT repeats). When the L/S distribution in patients and controls were compared, an increase of L alleles was observed among patients (49.9% vs. 39.7%; p = 0.02; p(c) = 0.04, odds ratio [OR] = 1.46; 95% confidence interval [CI], 1.06-2.01). Hence, the frequency of S alleles was decreased among patients (51.1% vs. 60.3%; p = 0.02; p(c) = 0.04; OR = 0.69; 95%CI, 0.50-0.95). Moreover, a statistically significant decrease in the frequency of S/S individuals was observed among RA patients (27.7% versus 40.7%; p = 0.01; p(c) = 0.03; OR = 0.56; 95%CI, 0.34-0.91). These differences were irrespective of the HLA "shared epitope" (SE) status, and were observed similarly among SE+ as well as among SE- patients. After combining these data with other reported previously by us, from studies of CTLA4 49 (A/G) and -318 (C/T) polymorphisms, we conclude that the strongest association between CTLA4 gene polymorphisms and RA susceptibility occurs with the 3' UTR polymorphism.
Rodríguez
M R
MR
Servico de Inmunología, Hospital Universitario Vergen del Rocío, Sevilla, Spain.
Núñez-Roldán
A
A
Aguilar
F
F
Valenzuela
A
A
García
A
A
González-Escribano
M F
MF
D020413:3' Untranslated Regions; D000069594:Abatacept; D000483:Alleles; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology*; D060908:CTLA-4 Antigen; D016022:Case-Control Studies; D018900:Dinucleotide Repeats; D005260:Female; D005787:Gene Frequency; D006801:Humans; D018796:Immunoconjugates; D008297:Male; D018598:Minisatellite Repeats; D011110:Polymorphism, Genetic; D013030:Spain
D020413:3' Untranslated Regions; D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D000069594:Abatacept