PDCD1 Single Nucleotide Polymorphisms in Iranian Patients With Juvenile Idiopathic Arthritis

Juvenile idiopathic arthritis (JIA) is a clinically heterogeneous cluster of complex diseases, in which both the genetic and environmental factors seem to play a role in the development of the disease. The current study aims to assess the association of programmed cell death 1 (PDCD1, also called PD-1) gene variants with JIA vulnerability in Iranian population. In this case-control association study, we investigated a group of 50 Iranian patients with JIA in comparison with 202 healthy controls and evaluated the frequency of alleles, genotypes, and haplotypes of PDCD1 single-nucleotide polymorphisms (SNPs), comprising PD-1.1 G/A, PD-1.3 G/A and PD-1.9 C/T, using PCR-RFLP method. Both the allelic and genotype frequencies of PD-1.1, PD-1.3 and PD-1.9 were similar in two groups of patients and controls. Moreover, no significant difference was observed between the two groups of patients and controls for GGC (PD-1.1 G, PD-1.3 G, PD-1.9 C), GAC (PD-1.1 G, PD-1.3 A, PD-1.9 C), and AGT (PD-1.1 A, PD-1.3 G, PD-1.9 T) haplotypes. Our results did not show any association between PDCD1 SNPs and the development of JIA in Iranian population

Evaluation of the association of single nucleotide polymorphisms in DDP4 and CDK5RAP2 genes with rheumatoid arthritis susceptibility in Iranian population

Background: Rheumatoid arthritis (RA) is known as a chronic autoimmune inflammatory disorder, which is characterized mainly by the progressive inflammation and destruction of the joints. In the pathogenesis of RA, a variety of cell types such as lymphocyte, dendritic cells, osteoclasts and synovial fibroblasts are involved. Genetic proneness has been implicated in the pathogenesis of RA. The aim of this study was to evaluate the association of single nucleotide polymorphisms (SNPs) in DPP4 and CDK5RAP2 genes and risk of RA in Iranian population. Methods: For genotyping, 623 RA patients and 412 healthy subjects were recruited. Genetic analysis of DPP4 gene rs12617656 and CDK5RAP2 gene rs12379034 polymorphisms was conducted using TaqMan allelic discrimination (for rs12617656) and ARMS-PCR (for rs12379034) methods. Results: Experiments demonstrated that alleles and genotypes of both SNPs were represented equally in RA patients and controls. Statistical analysis revealed that none of the rs12617656 and rs12379034 SNPs had significant differences in prevalence of both alleles and genotypes between RA patients and healthy controls. Conclusions: It appears that gene polymorphisms of DPP4 and CDK5RAP2 are not involved in the pathogenesis of RA in Iranian population. Keywords: Rheumatoid arthritis, Gene polymorphism, Inflammation, Autoimmunity, DPP4, CDK5RAP

Analysis of the genetic component of systemic sclerosis in Iranian and Turkish populations through a genome-wide association study

Objectives. SSc is an autoimmune disease characterized by alteration of the immune response, vasculopathy and fibrosis. Most genetic studies on SSc have been performed in European-ancestry populations. The aim of this study was to analyse the genetic component of SSc in Middle Eastern patients from Iran and Turkey through a genome-wide association study.Methods. This study analysed data from a total of 834 patients diagnosed with SSc and 1455 healthy controls from Iran and Turkey. DNA was genotyped using high-throughput genotyping platforms. The data generated were imputed using the Michigan Imputation Server, and the Haplotype Reference Consortium as a reference panel. A meta-analysis combining both case-control sets was conducted by the inverse variance method.Results. The highest peak of association belonged to the HLA region in both the Iranian and Turkish populations. Strong and independent associations between the classical alleles HLA-DRB1*11:04 [P = 2.10 x 10(-24), odds ratio (OR) = 3.14] and DPB1*13:01 (P = 5.37 x 10(-14), OR = 5.75) and SSc were observed in the Iranian population. HLA-DRB1*11:04 (P = 4.90 x 10(-11), OR = 2.93) was the only independent signal associated in the Turkish cohort. An omnibus test yielded HLA-DRB1 58 and HLA-DPB1 76 as relevant amino acid positions for this disease. Concerning the meta-analysis, we also identified two associations close to the genome-wide significance level outside the HLA region, corresponding to IRF5-TNPO3 rs17424921-C (P = 1.34 x 10(-7), OR = 1.68) and NFKB1 rs4648133-C (P = 3.11 x 10(-7), OR = 1.47).Conclusion. We identified significant associations in the HLA region and suggestive associations in IRF5-TNPO3 and NFKB1 loci in Iranian and Turkish patients affected by SSc through a genome-wide association study and an extensive HLA analysis