A new haplotype of PDCD1 is associated with rheumatoid arthritis in Hong Kong Chinese.
OBJECTIVE
The programmed death 1 (PD-1) molecule is a negative regulator of T cells, and a genetic association between PD-1 and systemic lupus erythematosus and rheumatoid arthritis (RA) in Caucasians has been reported. The aim of this study was to investigate the association of PDCD1 polymorphisms and haplotypes with RA in the Chinese population.


METHODS
Three single-nucleotide polymorphisms (SNPs), PD-1.1 G/A, PD-1.3 G/A, and PD-1.5 C/T, were genotyped in 180 patients with RA and 647 healthy controls in a case-control association study. Analyses of the association of genotypes and alleles with disease, haplotype construction, and linkage disequilibrium (LD) were performed.


RESULTS
We constructed haplotypes with the alleles of markers PD-1.1 G/A and PD-1.5 C/T and found that the GT haplotype was overrepresented in patients with RA (31%) compared with controls (23%) (P = 0.001, odds ratio [OR] 1.54, 95% confidence interval [95% CI] 1.18-1.99). Among GT double homozygotes the risk of RA was increased even further (OR 2.31, 95% CI 1.31-4.08, P = 0.006). We also observed that the AA genotype of SNP PD-1.1 was associated with a decreased risk for developing RA (OR 0.38, 95% CI 0.15-0.99, P = 0.034). No association for SNP PD-1.5 in RA was found, and SNP PD-1.3 was nonpolymorphic in the Chinese population.


CONCLUSIONS
Our results support the involvement of PDCD1 as a susceptibility gene for RA in the Chinese population.
Kong
Eric Kai-Pang
EK
The University of Hong Kong, Hong Kong SAR, China.
Prokunina-Olsson
Ludmila
L
Wong
Wilfred Hing-Sang
WH
Lau
Chak-Sing
CS
Chan
Tak-Mao
TM
Alarcón-Riquelme
Marta
M
Lau
Yu-Lung
YL
D000328:Adult; D015703:Antigens, CD; D000954:Antigens, Surface / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins; D001172:Arthritis, Rheumatoid / Q000208:ethnology / Q000235:genetics*; D002681:China / Q000208:ethnology; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics*; D006723:Hong Kong / Q000453:epidemiology; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D061026:Programmed Cell Death 1 Receptor; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015703:Antigens, CD; D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor