From the Division of Rheumatology, and Division of Human Genetics, Faculty of Health Sciences, and the Sydney Brenner Institute for Molecular Bioscience, University of the Witwatersrand, Johannesburg, South Africa; Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama, USA; University of Cape Town, Cape Town, South Africa.
N. Govind, PhD, Division of Rheumatology, University of the Witwatersrand; R.J. Reynolds, PhD, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham; B. Hodkinson, PhD, University of Cape Town; C. Ickinger, MBBCh, Division of Rheumatology, University of the Witwatersrand; M. Ramsay, PhD, Sydney Brenner Institute for Molecular Bioscience, and Division of Human Genetics, Faculty of Health Sciences, University of the Witwatersrand;S.L. Bridges Jr., PhD, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham; M. Tikly, PhD, Division of Rheumatology, University of the Witwatersrand.
J Rheumatol. 2019 Feb;46(2):138-144. doi: 10.3899/jrheum.180107. Epub 2018 Nov 1.
To investigate the association of specific amino acid positions, residues, and haplotypes of HLA-DRB1 in black South Africans with autoantibody-positive rheumatoid arthritis (RA).
High-resolution genotyping was performed in 266 black South Africans with autoantibody-positive RA and 362 ethnically and geographically matched controls. The alleles were converted to specific amino acid residues at polymorphic sites for downstream analyses. Logistic regression models were used to test whether variability at site, specific amino acid residues, and haplotypes (constructed from positions 11, 71, and 74) were associated with RA.
Of the 29 amino acid positions examined, positions 11, 13, and 33 (permutation p = 3.4, 1.2, and 2.1, respectively) showed the strongest association with RA. Univariate analyses of individual amino acid residues showed valine at position 11 (OR 5.1, 95% CI 3.7-7.0) and histidine at position 13 (OR 6.1, 95% CI 4.2-8.6) conferred the highest risk. The valine containing haplotypes of position 11, 71, 74, V_K_A conferred the most risk (OR 4.52, 95% CI 2.68-7.61) and conversely the haplotype with serine at this position, S_K_R, conferred the most protection (OR 0.83, 95% CI 0.61-1.15).
Autoantibody-positive RA in black South Africans is associated with histidine at position 13 and valine at position 11 of HLA-DRB1, and haplotypes with valine at position 11 conferred the highest risk; conversely, serine at position 11 conveyed protection.
探讨南非黑人中特定的 HLA-DRB1 氨基酸位置、残基和单倍型与自身抗体阳性类风湿关节炎（RA）的关联。
对 266 例南非黑人自身抗体阳性 RA 患者和 362 例具有相同种族和地理位置的匹配对照者进行高分辨率基因分型。将等位基因转换为多态性位点的特定氨基酸残基，用于下游分析。使用逻辑回归模型来检验在特定位置、特定氨基酸残基和单倍型（由位置 11、71 和 74 构建）上的变异性是否与 RA 相关。
在所检查的 29 个氨基酸位置中，位置 11、13 和 33（置换检验 p 值分别为 3.4、1.2 和 2.1）与 RA 的相关性最强。对单个氨基酸残基的单变量分析显示，位置 11 的缬氨酸（OR 5.1，95%CI 3.7-7.0）和位置 13 的组氨酸（OR 6.1，95%CI 4.2-8.6）的风险最高。位置 11、71、74 的缬氨酸单倍型 V_K_A 风险最高（OR 4.52，95%CI 2.68-7.61），相反，该位置的丝氨酸单倍型 S_K_R 风险最低（OR 0.83，95%CI 0.61-1.15）。
南非黑人的自身抗体阳性 RA 与 HLA-DRB1 位置 13 的组氨酸和位置 11 的缬氨酸相关，位置 11 的缬氨酸单倍型风险最高；相反，位置 11 的丝氨酸则提供保护。
