Department of Neurological medicine, Capital Institute of Pediatrics, Beijing, 100020, China.
Behav Brain Funct. 2013 Jan 29;9:6. doi: 10.1186/1744-9081-9-6.
Tryptophan hydroxylase-2 (TPH2) is a potential candidate gene for screening tic disorder (TD).
A case-control study was performed to examine the association between the TPH2 gene and TD. The Sequenom® Mass ARRAY iPLEX GOLD System was used to genotype two single nucleotide polymorphisms (SNPs) of the TPH2 gene in 149 TD children and in 125 normal controls.
For rs4565946, individuals with the TT genotype showed a significantly higher risk of TD than those with TC plus CC genotypes [odds ratio (OR) =3.077, 95% confidence interval (CI): 1.273-7.437; P = 0.009], as did male TD children with the TT genotype (OR = 3.228, 95% CI: 1.153-9.040; P = 0.020). The G allele of rs4570625 was significantly more frequent in TD children with higher levels of tic symptoms (Yale Global Tic Severity Scale, YGTSS) than those in controls among the male children (OR = 1.684, 95%: 1.097-2.583; P = 0.017]. TD children with severe tic symptoms had significantly higher frequencies of rs4546946 TT genotype than did normal controls in boys (OR = 3.292, 95% CI: 1.139-9.513; P = 0.022). We also found that genotype distributions of both SNPs were different between the Asian and European populations.
Our results indicated that the TT genotype of rs4565946 is a potential genetic risk factor for TD, and the allele G of rs4570625 might be associated with the severity of tic symptoms in boys. These polymorphisms might be susceptibility loci for TD in the Chinese Han population. Because of the confounding of co-existing attention deficit hyperactivity disorder (ADHD),these findings need to be confirmed by studies in much larger samples.
色氨酸羟化酶 2(TPH2)是筛选抽动障碍(TD)的潜在候选基因。
采用病例对照研究,检测 TPH2 基因与 TD 之间的关联。采用Sequenom® Mass ARRAY iPLEX GOLD 系统对 149 例 TD 患儿和 125 例正常对照的 TPH2 基因的两个单核苷酸多态性(SNP)进行基因分型。
对于 rs4565946,TT 基因型个体患 TD 的风险显著高于 TC+CC 基因型个体[比值比(OR)=3.077,95%置信区间(CI):1.273-7.437;P=0.009],男性 TD 患儿 TT 基因型的 OR=3.228,95%CI:1.153-9.040;P=0.020)。rs4570625 的 G 等位基因在男性 TD 患儿中,耶鲁整体抽动严重程度量表(Yale Global Tic Severity Scale,YGTSS)评分较高的患儿中比对照组更常见(OR=1.684,95%:1.097-2.583;P=0.017)。在男孩中,具有严重抽动症状的 TD 患儿 rs4546946 TT 基因型的频率明显高于正常对照组(OR=3.292,95%CI:1.139-9.513;P=0.022)。我们还发现,这两个 SNP 的基因型分布在亚洲和欧洲人群之间存在差异。
我们的结果表明,rs4565946 的 TT 基因型可能是 TD 的潜在遗传危险因素,rs4570625 的等位基因 G 可能与男孩的抽动症状严重程度有关。这些多态性可能是汉族人群 TD 的易感基因座。由于共患注意缺陷多动障碍(ADHD)的混杂因素,这些发现需要在更大的样本量研究中得到证实。