OBJECTIVE: To investigate the possible association of the CT60A/G marker with systemic lupus erythematosus (SLE) in Spanish patients, and to identify the possible CTLA4 haplotype responsible for the association, taking into account other polymorphisms described at positions -1722T/C, -319C/T, +49A/G, and the microsatellite (AT)(n) in the 3'-untranslated region (3'-UTR) of the CTLA4 gene. METHODS: Genotyping of CT60 was performed in 395 patients with SLE and 293 healthy controls using polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis. Genotyping of the rest of the dimorphisms has been previously reported. Genotyping of microsatellite polymorphism (AT)(n) in the 3'-UTR was performed using PCR with a fluorescence-labeled primer. RESULTS: With regard to CT60A/G, the frequency of the AA genotype was significantly decreased among the SLE patients (18.7% versus 28.3% in the control group; P = 0.003, corrected P [P(corr)] = 0.009, odds ratio [OR] = 0.58, 95% confidence interval [95% CI] 0.40-0.85). In other words, the frequency of individuals bearing the G phenotype was increased in the patient group compared with the control group (81.2% versus 71.7%; P = 0.003, P(corr) = 0.006, OR = 1.71, 95% CI 1.18-2.49). The distribution of allele frequency was also significantly different between patients and controls (P = 0.01, P(corr) = 0.02, OR [for allele G] = 1.32, 95% CI 1.06-1.65). After combining the data on the different polymorphisms, 2 neutral haplotypes were found: +49A;(AT)(7);CT60A and +49G;(AT)(8-19);CT60G. In addition, a susceptibility haplotype was found: +49A;(AT)(>19);CT60G. CONCLUSION: The 3'-UTR of the CTLA4 gene is involved in susceptibility to SLE.
OBJECTIVE: To investigate the possible association of the CT60A/G marker with systemic lupus erythematosus (SLE) in Spanish patients, and to identify the possible CTLA4 haplotype responsible for the association, taking into account other polymorphisms described at positions -1722T/C, -319C/T, +49A/G, and the microsatellite (AT)(n) in the 3'-untranslated region (3'-UTR) of the CTLA4 gene. METHODS: Genotyping of CT60 was performed in 395 patients with SLE and 293 healthy controls using polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis. Genotyping of the rest of the dimorphisms has been previously reported. Genotyping of microsatellite polymorphism (AT)(n) in the 3'-UTR was performed using PCR with a fluorescence-labeled primer. RESULTS: With regard to CT60A/G, the frequency of the AA genotype was significantly decreased among the SLEpatients (18.7% versus 28.3% in the control group; P = 0.003, corrected P [P(corr)] = 0.009, odds ratio [OR] = 0.58, 95% confidence interval [95% CI] 0.40-0.85). In other words, the frequency of individuals bearing the G phenotype was increased in the patient group compared with the control group (81.2% versus 71.7%; P = 0.003, P(corr) = 0.006, OR = 1.71, 95% CI 1.18-2.49). The distribution of allele frequency was also significantly different between patients and controls (P = 0.01, P(corr) = 0.02, OR [for allele G] = 1.32, 95% CI 1.06-1.65). After combining the data on the different polymorphisms, 2 neutral haplotypes were found: +49A;(AT)(7);CT60A and +49G;(AT)(8-19);CT60G. In addition, a susceptibility haplotype was found: +49A;(AT)(>19);CT60G. CONCLUSION: The 3'-UTR of the CTLA4 gene is involved in susceptibility to SLE.
Authors: Elena Sanchez; Ajay Nadig; Bruce C Richardson; Barry I Freedman; Kenneth M Kaufman; Jennifer A Kelly; Timothy B Niewold; Diane L Kamen; Gary S Gilkeson; Julie T Ziegler; Carl D Langefeld; Graciela S Alarcón; Jeffrey C Edberg; Rosalind Ramsey-Goldman; Michelle Petri; Elizabeth E Brown; Robert P Kimberly; John D Reveille; Luis M Vilá; Joan T Merrill; Juan-Manuel Anaya; Judith A James; Bernardo A Pons-Estel; Javier Martin; So-Yeon Park; So-Young Bang; Sang-Cheol Bae; Kathy L Moser; Timothy J Vyse; Lindsey A Criswell; Patrick M Gaffney; Betty P Tsao; Chaim O Jacob; John B Harley; Marta E Alarcón-Riquelme; Amr H Sawalha Journal: Ann Rheum Dis Date: 2011-06-30 Impact factor: 19.103
Authors: Irina Bonzheim; Eva Geissinger; Wen-Yu Chuang; Sabine Roth; Philipp Ströbel; Alexander Marx; Peter Reimer; Martin Wilhelm; Bernhard Puppe; Andreas Rosenwald; Hans Konrad Müller-Hermelink; Thomas Rüdiger Journal: J Hematop Date: 2008-04-24 Impact factor: 0.196
Authors: Paola Forabosco; Emmanuelle Bouzigon; Mandy Y Ng; Jane Hermanowski; Sheila A Fisher; Lindsey A Criswell; Cathryn M Lewis Journal: Eur J Hum Genet Date: 2008-09-10 Impact factor: 4.246
Authors: Javier Martin; Marta E Alarcón-Riquelme; Angélica M Delgado-Vega; Anna-Karin Abelson; Elena Sánchez; Torsten Witte; Sandra D'Alfonso; Mauro Galeazzi; Juan Jiménez-Alonso; Bernardo A Pons-Estel Journal: Genes Immun Date: 2008-12-18 Impact factor: 2.676
Authors: Lisa M Maier; David E Anderson; Philip L De Jager; Linda S Wicker; David A Hafler Journal: Proc Natl Acad Sci U S A Date: 2007-11-13 Impact factor: 11.205