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Article 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 and L (P1); E (P3); A , Y , I/S , T , I and E (P4); L , T , D and D (P9), whereas, the amino acids A and T (P1); S (P3); G , A and S (P4); H and T , S (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.
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