مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
Lysine at position 71, Proline at position 74 and Valine at position 11 in the HLA-DRB1 beta chain are associated with Rheumatoid arthritis
Lysine at position 71, Proline at position 74 and Valine at position 11 in the HLA-DRB1 beta chain are associated with Rheumatoid arthritis
Hadi Bazzazi,1,*Yaghoub Yazdani,2Mehrdad Aghaei,3
1. Department of Medical Laboratory Sciences, Go.C.,IslamicAzad University, Gorgan, Iran 2. Golestan University of Medical Sciences 3. Golestan Rheumatology Research Center (GRRC), Golestan University of Medical Sciences
Introduction: Objective: Rheumatoid arthritis (RA) is a complex multifactorial autoimmune disease in which genetic factors, particularly within the HLA-DRB1 region, play a pivotal role in disease susceptibility. This study aimed to compare the amino acid sequences of the shared epitope (SE) motif in the HLA-DRB1 molecule between RA patients and healthy individuals to identify residues associated with disease susceptibility or protection.
Methods: Materials and Methods: An observational case-control study was conducted involving 60 RA patients and 60 randomly selected healthy controls. Genomic DNA was extracted from peripheral blood samples, and the second exon of the HLA-DRB1 gene—encoding the β-chain—was amplified using PCR. Sequencing was performed, and Chromas software was used to analyze nucleotide sequences and translate them into amino acid sequences of the SE motif.
Results: Results: Significant differences were observed in the frequencies of amino acid residues at positions 71 (p < 0.01) and 74 (p < 0.05) of the HLA-DRB1 β-chain between RA patients and healthy controls. Lysine at position 71 was more prevalent among healthy individuals, indicating a protective role (OR = 0.500; p = 0.032). Similarly, proline at position 74 was significantly more frequent in healthy controls compared to anti-citrullinated peptide antibody (ACPA)-positive patients, also suggesting a protective effect (OR = 0.231; p = 0.032). Additionally, a statistically significant difference in the frequency of valine at position 11 was found between ACPA-positive patients and healthy controls (p < 0.05).
Conclusion: Conclusions: The findings highlight significant associations between specific amino acid residues at positions 11, 71, and 74 of the HLA-DRB1 β-chain and RA susceptibility or protection. These results support the potential role of fine-mapping HLA polymorphisms in understanding RA pathogenesis.