Association of the CT60 marker of the CTLA4 gene with systemic lupus erythematosus.
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.


CONCLUSIONS
The 3'-UTR of the CTLA4 gene is involved in susceptibility to SLE.
Torres
Belén
B
Hospital Universitario Virgen del Rocío, Seville, Spain.
Aguilar
Francisco
F
Franco
Ernesto
E
Sánchez
Elena
E
Sánchez-Román
Julio
J
Jiménez Alonso
Juan
J
Núñez-Roldán
Antonio
A
Martín
Javier
J
González-Escribano
María Francisca
MF
D020413:3' Untranslated Regions / Q000235:genetics; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D060908:CTLA-4 Antigen; D016022:Case-Control Studies; D016001:Confidence Intervals; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D018895:Microsatellite Repeats; D016017:Odds Ratio; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length
D020413:3' Untranslated Regions; D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D005819:Genetic Markers