Laboratory Sciences and Services Division (LSSD), icddr,b, Dhaka, 1212, Bangladesh.
Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, 1000, Bangladesh.
Ann Clin Transl Neurol. 2019 Sep;6(9):1849-1857. doi: 10.1002/acn3.50884. Epub 2019 Aug 30.
The etiology of Guillain-Barré syndrome (GBS) remains enigmatic, although genetic and environmental factors are speculated to be associated with this autoimmune condition. We investigated whether polymorphisms and the haplotype structures of the human leukocyte antigen (HLA)-DQB1 gene relate to the autoimmune response to infection and affect the development of GBS.
HLA-DQB1 polymorphic alleles (*0201, *030x, *0401, *050x, *060x) were determined for 151 Bangladeshi patients with GBS and 151 ethnically matched healthy controls using sequence-specific polymerase chain reaction. Pairwise linkage disequilibrium (LD) and haplotype patterns were analyzed based on D ́statistics and the genotype package in R statistics, respectively. Association studies were conducted using Fisher's exact test and logistic regression analysis. The Bonferroni method was applied to correct for multiple comparisons, whereby the P-value was multiplied with the number of comparisons and denoted as Pc (Pc, P corrected).
No associations were observed between HLA-DQB1 alleles and susceptibility to disease in the comparison between GBS patients and healthy subjects. Haplotype 9 (DQB1*0303-0601) tended to be less frequent among patients with GBS than healthy controls (P = 0.006, OR = 0.49, 95% CI = 0.30-0.82; Pc = 0.06). Haplotype 5 (DQB10501-0602) and the DQB10201 alleles were more frequent in the Campylobacter jejuni-triggered axonal variant of GBS (P = 0.024, OR = 4.06, 95% CI = 1.25-13.18; Pc = 0.24) and demyelinating subtype (P = 0.027, OR = 2.68, 95% CI = 1.17-6.17; Pc = 0.35), though these associations were not significant after Bonferroni correction.
This study indicates that HLA-DQB1 polymorphisms are not associated with susceptibility to GBS. In addition, these genetic markers did not influence the clinical features or serological subgroup in patients with C. jejuni-triggered axonal variant of GBS.
吉兰-巴雷综合征（GBS）的病因仍然难以捉摸，尽管遗传和环境因素被认为与这种自身免疫性疾病有关。我们研究了人类白细胞抗原（HLA）-DQB1 基因的多态性和单倍型结构是否与感染后的自身免疫反应有关，并影响 GBS 的发展。
采用序列特异性聚合酶链反应（PCR）检测 151 例孟加拉国 GBS 患者和 151 例匹配的健康对照者的 HLA-DQB1 多态性等位基因（*0201、*030x、*0401、*050x、*060x）。基于 D'统计和 R 统计中的基因型包，分别分析了连锁不平衡（LD）和单倍型模式。采用 Fisher 精确检验和 logistic 回归分析进行关联研究。采用 Bonferroni 法校正多重比较，即将 P 值乘以比较次数，并表示为 Pc（Pc，校正后的 P 值）。
在 GBS 患者与健康对照组之间的比较中，HLA-DQB1 等位基因与疾病易感性之间未观察到关联。与健康对照组相比，GBS 患者中 Hap1otype9（DQB1*0303-0601）的频率较低（P=0.006，OR=0.49，95%CI=0.30-0.82；Pc=0.06）。Hap1otype5（DQB10501-0602）和 DQB10201 等位基因在空肠弯曲菌触发的 GBS 轴索性变异型（P=0.024，OR=4.06，95%CI=1.25-13.18；Pc=0.24）和脱髓鞘亚型（P=0.027，OR=2.68，95%CI=1.17-6.17；Pc=0.35）中更为常见，但这些关联在经过 Bonferroni 校正后并不显著。
本研究表明，HLA-DQB1 多态性与 GBS 的易感性无关。此外，这些遗传标记并未影响空肠弯曲菌触发的 GBS 轴索性变异型患者的临床特征或血清学亚群。
