背景:先前的研究表明感染后自身免疫和免疫缺陷在Tourette综合征的发病机制中起重要作用。CARD8可以抑制炎症介质激活的NF-κB的活性。
目的:研究中国汉族人群CARD8基因rs2043211多态性与Tourette综合征易感性的关系。
方法:我们招募了279名诊断为Tourette综合征的患者及其父母进行研究。使用预先设计的TaqMan单核苷酸多态性基因分型试验对CARD8rs2043211单核苷酸多态性进行基因分型。使用传播不平衡检验和单倍型相对风险和基于单倍型的单倍型相对风险评估了这种单核苷酸多态性的遗传贡献。
结果:CARD8中rs2043211多态性的等位基因和基因型分布结果表明,Tourette综合征患者组和父母组均处于Hardy-Weinberg平衡状态。在突变等位基因传递中没有观察到显著差异(传递不平衡检验=1.107,df=1,p=0.322)。单倍型相对危险度分析结果显示,来自父母的Tourette综合征患者的基因型频率(AA/AT/TT)差异无统计学意义(单倍型相对危险度=1.152,χ(2)=0.494,p=0.482,95%CI=0.777-1.708)。同样,对基于单倍型的单倍型相对风险的分析也不支持来自父母的Tourette综合征患者的等位基因频率(A/T)的统计学显著关联(基于单倍型的单倍型相对风险=1.130,χ(2)=1.037,p=0.308,95%CI=0.893~1.429).
结论:我们的结果表明,CARD8可能在中国汉族人群抽动——抽动——综合征的发病机制中没有作用。然而,结果仍需要在更大的样本和不同的人群中进行测试。
BACKGROUND: Previous studies showed that postinfectious autoimmunity and immune deficiency played an important role in the pathogenesis of Tourette syndrome.
CARD8 can suppress activity of NF-ΚB activated by inflammatory mediators.
OBJECTIVE: To
study the association between the rs2043211 polymorphism in
CARD8 and susceptibility to Tourette syndrome in Chinese Han population.
METHODS: We recruited 279 patients diagnosed with Tourette syndrome and their parents for the
study. Genotyping for
CARD8 rs2043211 single-nucleotide polymorphism was performed using predesigned TaqMan single-nucleotide polymorphism genotyping assay. The genetic contribution of this single-nucleotide polymorphism was evaluated using transmission disequilibrium test and haplotype relative risk and the haplotype-based haplotype relative risk.
RESULTS: The results of the allelic and genotypic distribution of rs2043211 polymorphism in
CARD8 showed that both the Tourette syndrome patients group and the parents group are in Hardy-Weinberg equilibrium. No significant differences were observed in the mutant allele transmission (transmission disequilibrium test = 1.107, df = 1, p = 0.322). Results of haplotype relative risk analysis showed that no statistical significant difference was found in the genotypic frequency (AA/AT/TT) of Tourette syndrome patients passed from parents (haplotype relative risk = 1.152, χ(2 )= 0.494, p = 0.482, 95% CI = 0.777-1.708). Similarly, the analysis of haplotype-based haplotype relative risk was also not to support a statistically significant association in allelic frequency (A/T) of Tourette syndrome patients passed from parents (haplotype-based haplotype relative risk = 1.130, χ(2 )= 1.037, p = 0.308, 95% CI = 0.893-1.429).
CONCLUSIONS: Our results suggest CARD8 might not play a role in the pathogenesis of Tourette syndrome in Chinese Han population. However, the results still need to be tested in a larger sample and different populations.