Association of single nucleotide polymorphisms (rs4565946 and rs4570625) of tryptophan hydroxylase2 gene with Tourette's syndrome / 中华神经医学杂志

ABSTRACT

Objective To investigate the association of single nucleotide polymorphisms (SNPs,rs4565946 and rs4570625) of tryptophan hydroxylase2 (TPH2) gene with Tourette's syndrome (TS) in Beijing Han population.Methods One hundred and forty-nine patients with TS,diagnosed and treated in our hospital from January 2009 to January 2011,were chosen; these patients were sub-divided into mild symptoms group (n=25) and moderate to severe symptoms group (n=87) according to the scores of Yale Global Tic Severity Scale (YGTSS); another 125 healthy children,collected at the same time period,were used as control group.MassARRAY iPLEX GOLD System was used to detect the two SNPs (rs4570625 and rs4565946) of TPH2 gene.Genotype distribution and allele fiequencies of these two group patients were compared.Transcription factor binding sites of TPH2 gene polymorphisms were analyzed by the web site of transcription factor binding sites for function prediction.Results For rs4565946,individuals with the TT genotype showed a significantly higher risk of TS than those with TC plus CC genotypes (OR=3.077,95％CI:1.273-7.437; P＜0.05); as did male TS children with the TT genotype (OR=3.228,95％ CI:1.153-9.040; P＜0.05).Further association analyses showed that G allele of rs4570625 in children of moderate to severe symptoms group had significantly higher frequency than that in controls among the male children (OR=1.684,95％:1.097-2.583; P＜0.05).Children of moderate to severe symptoms group had significantly higher frequencies of rs4546946 TT genotype than normal controls in males (OR=3.292,95％ CI:1.139-9.513; P＜0.05).Bioinformatics method indicated that the G genotype of rs4570625 mutated from T genotype might affect the binding ability of its transcription factor with its promoter in TPH2 gene.Conclusions TT genotype of rs4565946 is a potential genetic risk factor for TS.Allele G ofrs4570625 might be associated with the severity of tic symptoms in boys.These polymorphisms might be susceptibility loci for TS.