Biological relevance of the polymorphism in the CCR5 gene in refractory and non-refractory rheumatoid arthritis in Mexicans.
OBJECTIVE
The aim of this study was to analyze the frequencies of the CCR5 delta 32 deletion and HLA class II alleles in Mexican Amerindian populations and its relevance in the development and severity of RA.


METHODS
We studied 212 Mexican Mestizo subjects (40 patients with refractory RA, 102 patients with non-refractory RA and 70 healthy individuals). At the same time, to evaluate the ethnicity of the CCR5 delta 32 deletion we also studied 192 individuals from three Mexican Amerindian populations (70 Mayo (Capomo) individuals, 61 Teenek individuals, and 61 Mazatecan Indians). The delta 32 deletion in the CCR5 structural gene and HLA-DRB1 were determined by a PCR-SSP and a PCR-SSO procedure, respectively.


RESULTS
In the non-refractory RA group the CCR5 delta 32 gene frequency was 0.019 and the following genotype frequencies were observed: CCR5/CCR5 = 98.0%, CCR5/CCR5 delta 32 = 1.9% and CCR5 delta 32/CCR5 delta = 1.0%. In the refractory RA group the CCR5 delta 32 gene frequency was 0.025 and the genotype distribution was similar to that in the non-refractory RA group. The deletion was not detected in the Mexican Mestizo healthy group, or among the Teenek and Mayo Amerindians, all being individuals homozygous for the wild type allele. In the Mazatecan group the deletion frequency was 1.6% (g.f. = 0.016). We observed a significant increase in the frequency of the DRB1*07 allele in severe RA patients in relation to the non-severe RA group (p = 0.02, OR = 5.65, 95% CI = 0.95-43.05).


CONCLUSIONS
Our results suggest that the CCR5 delta 32 deletion is not common in Mexican Amerindian populations and this study does not support an important role of CCR5 delta 32 in the pathogenesis of RA or a severe form of the disease in Mexicans.
Zúñiga
J A
JA
Molecular Biology and Immunogenetics Laboratory, Infectious Diseases Unit, Instituto Nacional de Enfermedades Respiratorias, Calzada Tlalpan 4502, Tlalpan 14080, Mexico, D.F. joazu@yahoo.com
Villarreal-Garza
C
C
Flores
E
E
Barquera
R
R
Pérez-Hernández
N
N
Montes de Oca
J V
JV
Cardiel
M H
MH
Vargas-Alarcón
G
G
Granados
J
J
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000503:physiopathology; D001483:Base Sequence; D016022:Case-Control Studies; D016001:Confidence Intervals; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006684:HLA-DR Antigens / Q000032:analysis; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011336:Probability; D019713:Receptors, CCR5 / Q000235:genetics*; D012016:Reference Values; D012494:Sampling Studies; D012720:Severity of Illness Index
D006684:HLA-DR Antigens; D019713:Receptors, CCR5