부산대학교 도서관

Background: Rheumatoid arthritis (RA) is an autoimmune, inflammatory disease, caused by environmental and genetic factors. Aim: To elucidate the association of human leukocyte antigen (HLA)‐DRB1*/DQB1* alleles/haplotypes and the variations of polymorphic amino acid changes in peptide binding pockets in RA patients from south India. Methods: HLA typing was performed in 176 RA patients and 176 healthy controls by polymerase chain reaction—sequence‐specific primers method. Results: Strong susceptible association for alleles such as DRB1*04:01(odds ratio [OR] = 3.66), 04:06 (OR = 3.81), 03:01 (OR = 2.93), 06:01 (OR = 2.53) and protective association for alleles such as DRB1*13:01 (OR = 0.17), 14:01 (OR = 0.15), 05:02 (OR = 0.17), and 05:03 (OR = 0.338) were observed in RA patients. The 2‐locus haplotypes such as 04‐02:01 (OR = 3.844), 04‐06:01 (OR = 6.57), 07‐03:01 (OR = 6.16), 07‐06:01 (OR = 3.42), 12‐06:01 (OR = 5.24), 15‐03:01 (OR = 4.69) with susceptible and DRB1*14‐DQB1*05:03 (OR = 0.078) with protective associations were observed in RA patients. The acid‐base analysis revealed that the basic group BB allele was positively associated (OR = 2.372) and the acidic group AA allele was negatively associated (OR = 0.086). The analysis on shared epitopes has revealed that the combination QKRAA+, (Q)RRAA+ or (Q)RRAA− was positively associated with RA (OR = 2.78). The amino acid variation at HLA‐DQβ molecule revealed susceptible associations for residues E86 and L87 (P1); E74 (P3); A13, Y26, I/S28, T28, I71 and E74 (P4); L9, T30, D37 and D57 (P9), whereas, the amino acids A86 and T87 (P1); S74 (P3); G13/26, A71 and S74 (P4); H30 and T37, S57 (P9), showed protective associations. Conclusions: Alleles DRB1*04:06 and*04:01 showed strong susceptible and DRB1*13:01 and *14:01 showed protective associations in RA patients. The amino acid variations in DQβ molecules revealed significant molecular markers for susceptibility to and protection from RA in south India. [ABSTRACT FROM AUTHOR]