Department of Immunology, Madurai Kamaraj University, Madurai, India.
Texas Tech University Health Sciences Center, Lubbock, Texas.
Int J Rheum Dis. 2019 Aug;22(8):1553-1562. doi: 10.1111/1756-185X.13612. Epub 2019 Jun 6.
Rheumatoid arthritis (RA) is an autoimmune, inflammatory disease, caused by environmental and genetic factors.
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.
HLA typing was performed in 176 RA patients and 176 healthy controls by polymerase chain reaction-sequence-specific primers method.
Strong susceptible association for alleles such as DRB104:01(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 DRB113:01 (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 DRB114-DQB105:03 (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.
Alleles DRB104:06 and04:01 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.
类风湿关节炎（RA）是一种由环境和遗传因素引起的自身免疫性炎症性疾病。
阐明人类白细胞抗原（HLA）-DRB1*/DQB1*等位基因/单倍型与印度南部 RA 患者肽结合口袋中多态性氨基酸变化的相关性。
采用聚合酶链反应-序列特异性引物法对 176 例 RA 患者和 176 例健康对照者进行 HLA 分型。
RA 患者中观察到某些等位基因存在强易感关联，如 DRB104:01（比值比 [OR] = 3.66）、04:06（OR = 3.81）、03:01（OR = 2.93）、06:01（OR = 2.53），以及某些等位基因存在保护性关联，如 DRB113:01（OR = 0.17）、14:01（OR = 0.15）、05:02（OR = 0.17）和 05:03（OR = 0.338）。RA 患者中观察到 2 个基因座的单倍型存在易感关联，如 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），而 DRB114-DQB105:03（OR = 0.078）则存在保护性关联。酸碱性分析显示，碱性基团 BB 等位基因呈正相关（OR = 2.372），酸性基团 AA 等位基因呈负相关（OR = 0.086）。对共享表位的分析表明，QKRAA+、（Q）RRAA+或（Q）RRAA-组合与 RA 呈正相关（OR = 2.78）。HLA-DQβ分子上的氨基酸变异显示，残基 E 和 L（P1）、E（P3）、A、Y、I/S、T、I 和 E（P4）、L、T、D 和 D（P9）存在易感性，而残基 A 和 T（P1）、S（P3）、G、A 和 S（P4）、H 和 T、S（P9）存在保护性。
DRB104:06 和04:01 等位基因在 RA 患者中表现出强烈的易感关联，而 DRB113:01 和14:01 则表现出保护关联。DQβ分子中的氨基酸变异揭示了印度南部 RA 易感性和保护的重要分子标志物。
