A new haplotype of PDCD1 is associated with rheumatoid arthritis in Hong Kong Chinese

Abstract

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.Conclusion. Our results support the involvement of PDCD1 as a susceptibility gene for RA in the Chinese population.

Association between a PD-1 gene polymorphism and antisperm antibody-related infertility in Iranian men

“…The cross-reactivity of ASAs with other auto-antibodies, including antithymocyte antibody, antinuclear antibody, antiphospholipid antibody, demonstrated in other studies [19], suggesting a polyclonal B-cell activation, similar to that seen in other autoimmune diseases (e.g. lupus erythematous) might implicate in the development of ASA-related infertility.…”

“…Previous studies have shown that PD-1 gene polymorphisms are correlated with autoimmune diseases such as ankylosing spondylitis [17], rheumatoid arthritis [10], and systemic lupus erythematous [20]. Moreover PD 1.3 SNP has been reported in different autoimmune settings, including rheumatoid arthritis [14], Type I diabetes [11], Multiple sclerosis [15], Ankylosing spondylitis [16] and Allergy [17].…”

“…To date, more than 30 SNPs have been identified in human PD-1 gene [10,11]. Prokunina et al reported that the allele A of a SNP named PD1.3 (PD1.3A) in intron 4 is associated with the development of SLE in Europeans (relative risk=2.6) and Mexicans (relative risk=3.5) [12] To date, Single Nucleotide Polymorphism association with PD 1.3 has been reported in several auto-antibody associated autoimmune diseases; including psoriasis [13], rheumatoid arthritis [14], Type I diabetes [11], Multiple sclerosis [15], Ankylosing spondylitis [16] and Allergy [17].…”

Defective CD8+CD28− regulatory T cell suppressor function in rheumatoid arthritis is restored by tumour necrosis factor inhibitor therapy

“…While autoimmune diseases have been linked with genetic polymorphisms of co-stimulatory markers [21,22], the functional implications have not yet been fully deciphered. Genetic polymorphism, of course, may compromise not only the function of these molecules but their detection by antibodies.…”

Failure to confirm association between PDCD1 polymorphisms and rheumatoid arthritis in a Japanese population

“…A recent study by Kong et al demonstrated that SNP PD-1.3 was nonpolymorphic among both patients with RA and controls in Hong Kong Chinese, and that PD-1.1 G/ A in the promoter (position -531 from the translation start) was associated with RA patients in their population. They also investigated whether the haplotype containing PD-1.1G and PD-1.5T was a risk factor for RA (Kong et al 2005).…”