Association of a programmed death 1 gene polymorphism with the development of rheumatoid arthritis, but not systemic lupus erythematosus.
OBJECTIVE
The expression of autoimmunity in mice deficient in programmed death 1 (PD-1) suggests that PD-1 is a candidate gene involved in the development of human autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). We therefore tested the potential association between PD-1 and the development of SLE and RA by conducting case-control genetic-association studies.


METHODS
Ninety-eight SLE patients, 84 RA patients, and sex-matched control subjects for each disease group were recruited and genotyped for a single-nucleotide polymorphism, C+872T, in the human PD-1 gene. The significance of the association of the PD-1 gene with SLE or with RA was analyzed by statistical tests for the difference in genotype distribution between disease and control groups.


RESULTS
The human PD-1 gene was found to be significantly associated with disease development in RA patients, but not SLE patients. The risk of RA development appeared to be significantly increased by carriage of the T allele (odds ratio 3.32, P < 0.0001) or the C/T genotype (odds ratio 3.52, P < 0.00005).


CONCLUSIONS
The PD-1 gene is significantly associated with RA susceptibility, suggesting the possibility that PD-1 may contribute to the pathogenesis of RA.
Lin
Shih-Chang
SC
Cathay General Hospital, Taipei, Taiwan.
Yen
Jeng-Hsien
JH
Tsai
Jaw-Ji
JJ
Tsai
Wen-Chen
WC
Ou
Tsan-Teng
TT
Liu
Hong-Wen
HW
Chen
Chung-Jen
CJ
D000483:Alleles; D015703:Antigens, CD; D000954:Antigens, Surface / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D003596:Cytosine; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D061026:Programmed Cell Death 1 Receptor; D012307:Risk Factors; D013941:Thymine
D015703:Antigens, CD; D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D003596:Cytosine; D013941:Thymine