Association of PDCD1 with susceptibility to systemic lupus erythematosus: evidence of population-specific effects.
OBJECTIVE
The A allele of the PD1.3 single-nucleotide polymorphism (SNP) on the programmed cell death gene PDCD1 was markedly more frequent in patients with systemic lupus erythematosus (SLE) than in unaffected controls in a recent study involving large sets of Swedish, European American, and Mexican families. This study sought to determine the role of PDCD1 in susceptibility to SLE in the Spanish population.


METHODS
Seven PDCD1 SNPs were studied in 518 SLE patients and 800 healthy control subjects who had been recruited in 5 distant towns spanning continental Spain. Patients and controls were of Spanish ancestry. The diagnosis of SLE was in accordance with the American College of Rheumatology updated classification criteria.


RESULTS
The A allele of the PD1.3 polymorphism was significantly less frequent in Spanish female patients with SLE than in Spanish female controls (9.0% versus 13.0%, odds ratio 0.67, 95% confidence interval 0.50-0.89). This difference was consistent across the 5 sets of samples grouped by town of recruitment. The other PDCD1 SNPs were not associated with SLE susceptibility. The haplotype structure of PDCD1 in the Spanish controls was different from that reported in other healthy control populations.


CONCLUSIONS
Our results confirm the association of PDCD1 with susceptibility to SLE, but the findings show a lack of involvement of the PD1.3 SNP, which is contrary to the role of the PD1.3 A allele observed previously. These contradictory results probably reflect population differences in the haplotype structure of the PDCD1 locus. More research focusing on new polymorphisms and identifying associations in other populations will be needed to clarify the role of PDCD1 in SLE susceptibility.
Ferreiros-Vidal
Isabel
I
Hospital Clinico Universitario de Santiago de Compostela, Santiago de Compostela, Spain.
Gomez-Reino
Juan J
JJ
Barros
Francisco
F
Carracedo
Angel
A
Carreira
Patricia
P
Gonzalez-Escribano
Francisca
F
Liz
Myriam
M
Martin
Javier
J
Ordi
Josep
J
Vicario
Jose L
JL
Gonzalez
Antonio
A
D000483:Alleles; D015703:Antigens, CD; D000954:Antigens, Surface / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D061026:Programmed Cell Death 1 Receptor; D013030:Spain; D044465:White People / Q000235:genetics
D015703:Antigens, CD; D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor