No primary association of MICA polymorphism with systemic lupus erythematosus.
OBJECTIVE
To replicate the described association between MHC class I chain-related A (MICA) gene polymorphism and susceptibility to systemic lupus erythematosus (SLE).


METHODS
MICA transmembrane microsatellite polymorphism was genotyped using a polymerase chain reaction (PCR)-based method. Genotyping of HLA-B* and DRB1* was performed using PCR and detection with a reverse sequence-specific oligonucleotide (SSO) probe system. Combined data for these three loci (HLA-B*, DRB1* and MICA) were obtained from a total of 333 patients and 361 healthy controls.


RESULTS
Significant association with B*08 [P < 10(-7), odds ratio (OR) 3.17, 95% confidence interval (CI) 2.02-5.00], DRB1*0301 (P < 10(-7), OR 2.07, 95% CI 1.59-2.68) and MICA5.1 (P = 0.01, OR 1.23, 95% CI 1.04-1.46) was observed. The combinations DRB1*0301-MICA5.1-B8 and HLA-DRB1*0301-B*08-positive and MICA5-1-negative were more frequent among SLE patients (11.4 vs 3.3% in healthy controls, P = 3.9 x 10(-5), OR 3.76, 95% CI 1.85-7.73, and 6.9 vs 1.7%, P = 0.0007, OR 4.32, 95% CI 1.68-13.10, respectively). Additionally, individuals who were HLA-DRB1*0301-B*08-negative and MICA5-1-positive were less frequent among patients (22.2 vs 31.3% in healthy controls, P = 0.007, OR 0.63, 95% CI 0.44-0.89) and the magnitude of the OR was similar to that obtained in individuals negative for all the three factors (OR 0.69, 95% CI 050-0.94). Further analysis performed to detect independent association strongly suggested that the association between MICA5.1 and SLE is secondary to the linkage disequilibrium of this allele with B*08.


CONCLUSIONS
Our results do not support an independent association of MICA gene polymorphism with susceptibility to SLE.
Instituto de Biomedicina, CSIC, Hospital Virgen de las Nieves, Granada, Spain.
E
E
Sánchez
B
B
Torres
J R
JR
Vilches
M A
MA
López-Nevot
N
N
Ortego-Centeno
J
J
Jiménez-Alonso
M A
MA
González-Gay
E
E
de Ramón
J
J
Sánchez-Román
A
A
Núñez-Roldán
J
J
Martín
M F
MF
González-Escribano
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015235:HLA-B Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
D015235:HLA-B Antigens; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553502:HLA-DRB1*03:01 antigen; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A