1. Association of HLA class II alleles/haplotypes and amino acid variations in the peptide binding pockets with rheumatoid arthritis.
- Author
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Chinniah R, Rajendran MS, Sivanadham R, Adaikalam ML, Ravi PM, Vijayan M, Boopathy S, Pandi S, Sevak V, and Karuppiah B
- Subjects
- Adult, Arthritis, Rheumatoid immunology, Arthritis, Rheumatoid metabolism, Binding Sites, Case-Control Studies, Epitopes immunology, Epitopes metabolism, Female, Gene Frequency, Genetic Predisposition to Disease, HLA-DQ beta-Chains metabolism, HLA-DRB1 Chains metabolism, Humans, India, Male, Middle Aged, Phenotype, Protective Factors, Protein Binding, Risk Assessment, Risk Factors, Arthritis, Rheumatoid genetics, Epitopes genetics, HLA-DQ beta-Chains genetics, HLA-DRB1 Chains genetics, Haplotypes
- Abstract
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 E
86 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., (© 2019 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)- Published
- 2019
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