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SAT0063 Association of the Programmed Death 1 Gene Polymorphism with the Development of Rheumatoid Arthritis in the Population of South-Eastern Poland
  1. A. Siwiec1,
  2. M. Majdan1,
  3. M. Ciesielka2,
  4. R. Mlak3,
  5. T. Krajka4
  1. 1Department of Rheumatology and Connective Tisseu Diseases, Medical University of Lublin
  2. 2The Forensic Medicine Department, Medical University of Lublin
  3. 3Chair and Department of Human Physiology, Medical University of Lublin
  4. 4Department of Mathematics, Lublin University of Technology, Lublin, Poland., LUBLIN, Poland

Abstract

Background Polymorphism of the PDCD1 gene are significantly associated with development of rheumatoid arthritis (RA), which may indicate the participation of the PD-1 (the programmed cell death 1) protein in the pathogenesis of the disease. There is a growing interest in the importance of the PD-1 in the maintenance of immunological balance and its role in the development of autoimmune diseases such as RA.

Objectives We estimate the incidence and association of polymorphic forms for PD-1 protein gene in patients with RA and healthy controls in the population of South-Eastern Poland.

Methods The distribution of genotypes in both patients' group (260 patients with RA) and the control group (100 subjects: 50 women and 50 men) were found to be Hardy-Weinberg equilibrium. In our study SNPs: PD-1.1 (rs36084323) G/A, PD-1.3 (rs11568821) G/A, PD-1.5 (rs2227981) C/T, PD-1.6 (rs10204525) G/A, PD-1.7 (rs41386349) C/T, PD-1.9 (rs2227982) C/T were examined by SNaPshot technique. Multiplex minisequencing reaction was performed with designed primers, basing on the sequences associated with 6 SNPs loci and with using kits ABI PRISM R SNAPShot ® Multiplex Kit (Applied Biosystems).The genotypes and the alleles of RA patients and the controls were analyzed by Fisher's exact test. Furthermore, the chi-square test and the Odds Ratio (OR) with Confidence Interval (CI) were computed for statistical analysis.

Results PD-1.5 C/T and PD-1.9 C/T polymorphisms affected the possibilities of RA occurrence in all the population. There was a significant difference in the distribution of genotype frequencies in RA patients compared with controls, for: SNP PD-1.5, with reduced frequency of CC genotype in RA patients (0.22 and 0.32 in those groups, p=0.0401), however SNP PD-1.9 frequency of CC genotype was higher in patients with RA when compared to the controls (0.99 and 0.94 in those groups, p=0.0160). The calculated odds ratio (OR) for RA patients having the CC genotyp of SNP PD-1.5 (versus CT or TT genotype) was 0,5785 (95% CI 0.3358-1.0049; p=0.0401;) and the p-value remained statistically significant. Thus the absence of homosygosity CC of SNP PD-1.5 affected the possibilities of RA occurrence. The calculated odds ratio (OR) for RA patients having the CC genotyp of SNP PD-1.9 (versus CT or TT genotype) was 5.4374 (95% CI 1.1343-34.2519; p=0.0160) and the p-value remained statistically significant. Thus the possession of homosygosity CC of SNP PD-1.9 affected the possibilities of RA development. We did not observe any significant difference in allele and genotype frequencies of PD-1.1 (rs36084323) G/A, PD-1.3 (rs11568821) G/A, PD-1.6 (rs10204525) G/A, PD-1.7 (rs41386349) C/T polymorphisms between the RA patients and the controls.

Conclusions In our study, we confirmed that homozygotes PD-1.5 CC and PD-1.9 CC are associated with RA occurrence. However, more genetic and immunological studies are needed to better explain the participation of the PD-1 protein in the autoimmune process.

Disclosure of Interest None declared

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