Association of HLA class II alleles/haplotypes and amino acid variations in the peptide binding pockets with rheumatoid arthritis
| Autor: | Meenakshi Sundari Rajendran, Padma Malini Ravi, Vandit Sevak, Balakrishnan Karuppiah, Seerala Boopathy, Murali Vijayan, Sasiharan Pandi, Ramgopal Sivanadham, Rathika Chinniah, Muthu Lakshmi Adaikalam |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male India Peptide binding Human leukocyte antigen Risk Assessment Epitope Arthritis Rheumatoid Epitopes Gene Frequency Rheumatology Risk Factors HLA-DQ beta-Chains Humans Medicine Genetic Predisposition to Disease Allele chemistry.chemical_classification Binding Sites business.industry Haplotype Odds ratio Middle Aged Protective Factors medicine.disease Molecular biology Amino acid Phenotype Haplotypes chemistry Case-Control Studies Rheumatoid arthritis Female business HLA-DRB1 Chains Protein Binding |
| Zdroj: | International Journal of Rheumatic Diseases. |
| ISSN: | 1756-185X 1756-1841 |
| Popis: | 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-DQ beta molecule revealed susceptible associations for residues E-86 and L-87 (P1); E-74 (P3); A(13), Y-26, I/S-28, T-28, I-71 and E-74 (P4); L-9, T-30, D-37 and D-57 (P9), whereas, the amino acids A(86) and T-87 (P1); S-74 (P3); G(13/26), A(71) and S-74 (P4); H-30 and T-37, S-57 (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 DQ beta molecules revealed significant molecular markers for susceptibility to and protection from RA in south India. |
| Databáze: | OpenAIRE |
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