Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
Hum Immunol. 2010 Sep;71(9):905-10. doi: 10.1016/j.humimm.2010.06.013. Epub 2010 Jun 19.
Tumor necrosis factor-alpha (TNF-alpha) polymorphisms with increased expression is associated with many autoimmune and inflammatory diseases. Possible role of TNF-alpha polymorphism in the pathogenesis of Guillain-Barré syndrome (GBS) largely remains unknown. We investigated polymorphisms in the promoter region of TNF-alpha gene and its expression in GBS patients and healthy controls. TNF-alpha (-308 G>A, -857 C>T, and -863 C>A) polymorphisms in 140 GBS patients and 206 healthy controls were studied using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele specific-PCR. TNF-alpha level in serum by ELISA was determined in 60 patients and an equal number of controls. Prevalence of TNF-alpha -308 G > A polymorphic A allele was associated with increased risk of GBS (p < 0.001; OR = 2.58, 95% CI = 1.61-4.14). Heterozygous genotype (G/A) had an association with acute motor axonal neuropathy (p < 0.001; OR = 4.23, 95% CI = 2.00-8.95) and variant genotype A/A with both axonal subtypes, acute motor axonal neuropathy (p = 0.015, OR = 7.00, 95% CI = 1.46-33.57) and acute motor sensory axonal neuropathy (p = 0.017; OR = 7.73, 95% CI = 1.44-41.37). Variant genotype T/T of TNF-alpha -857 C>T polymorphism was also significantly associated with acute motor axonal neuropathy (p = 0.034; OR = 3.93, 95% CI = 1.11-13.91). Patients with A and T alleles had higher TNF-alpha level in serum. TNF-alpha -308 G > A and -857 C>T (only T/T) polymorphisms with increased TNF-alpha level may predict susceptibility to axonal subtypes of GBS.
肿瘤坏死因子-α（TNF-α）的表达增加与许多自身免疫性和炎症性疾病有关。TNF-α 多态性在吉兰-巴雷综合征（GBS）发病机制中的可能作用在很大程度上仍然未知。我们研究了 GBS 患者和健康对照者 TNF-α 基因启动子区域的多态性及其表达。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）和等位基因特异性-PCR 检测 140 例 GBS 患者和 206 例健康对照者的 TNF-α（-308 G＞A、-857 C＞T 和-863 C＞A）多态性。通过 ELISA 测定 60 例患者和相同数量的对照者血清中的 TNF-α 水平。TNF-α-308 G＞A 多态性 A 等位基因的患病率与 GBS 风险增加相关（p＜0.001；OR=2.58，95%CI=1.61-4.14）。杂合基因型（G/A）与急性运动轴索性神经病（p＜0.001；OR=4.23，95%CI=2.00-8.95）有关，而变异基因型 A/A 与急性运动轴索性神经病（p=0.015，OR=7.00，95%CI=1.46-33.57）和急性运动感觉轴索性神经病（p=0.017；OR=7.73，95%CI=1.44-41.37）有关。TNF-α-857 C＞T 多态性的变异基因型 T/T 也与急性运动轴索性神经病显著相关（p=0.034；OR=3.93，95%CI=1.11-13.91）。携带 A 和 T 等位基因的患者血清 TNF-α 水平较高。TNF-α-308 G＞A 和-857 C＞T（仅 T/T）多态性与 TNF-α 水平升高可能预测 GBS 的轴索性亚型易感性。
