A Study On The Polymorphism Of DRD4exonⅢ 48bp VNTR, DAT1, COMTmet/val, IL-1Ra86bp, IL-1βexon5 Gene And Cognitive Function In Han Chinese Children With Tourette's Syndrome

[Objective] Gilles de la Tourette's syndrome (GTS) is a childhood-onset neuro- psychiatric disorder characterised by multiple motor and vocal tics lasting more than one year. The new prevalence of this syndrome is estimated to be between 1 and 3.8 per 1000 children and adolescents and the outcome is generally favourable. Affected individuals are at increased risk of various comorbid neurobehavioural problems, the negative effects of which commonly exceed those of tics. Despite evidence that TS is an inherited disorder, the exact genetic abnormality is unknown. Dopaminergic hypotheses have included abnormalities of both pre- and postsynaptic function in GTS. Family and twin studies provide substantial evidence for genetic factors being implicated in the occurrence of GTS. Recent evidence, however, suggests a prefrontal dopaminergic abnormality in children with GTS. An immune-mediated mechanism involving molecular mimicry has been proposed for PANDAS (Paediatric autoimmune neuropsychiatricdisorders associated with streptococcal infection). PANDAS may offer a new way to explore the pathogens of GTS. Significant data, however, support the concept that TS is a neurological disorder associated with frontal-subcortical pathways. In this paper, DRD4exonⅢ48bp VNTR,DAT1, COMTmet/val, IL-1Ra86bp,IL-1βexon5 gene Polymorphism and Cognitive Function are studied in Children with Tourette's Syndrome.[Method] 1. In the present study, we genotyped a large multiplex sample of GTS affected children for polymorphisms in DRD4exonⅢ48bp VNTR, DAT1, COMT met/val, IL-1Ra86bp,IL-1βexon5 genes. Associations were tested by the transmission disequilibrium test (TDT). 2. 86 Han Chinese children with GTS were tested using a set of neuropsychological test(Stroop test, trail making test, verbal fluency test, modified Wisconsin Card sorting test) and compared with 51 healthy control group to understand the relationship between cognitive deficits and genetics. 3. To investigate psychological problems in GTS, Conners Scale was applied in children with GTS and normal children. 4. Psychological tests above-mentioned were used to study the cognitive function in GTS parents.[Result] 1. No evidence for transmission disequilibrium was found for polymorphisms of DRD4exonⅢ48bp VNTR,DAT1,COMTmet/val, IL-1 Ra86bp,IL-1 βexon5 gene in this GTS sample. 2. DRD4exonⅢ48bp VNTR was significantly associated with GTS plus attention-deficit/hyperactivity disorder (+ADHD). The frequency of 410bp/240bp genotype and 240bp allele in combined ADHD were significantly different from GTS alone. 3. Compared with normal children, The GTS group showed impairment on almost all psychological measures. In some stroop test, combined ADHDgroup differed from the GTS-alone group. 4. Subjects with the met/met COMT genotype made significantly fewer perseverative errors on the Wisconsin Card Sorting Test than did subjects with the val/val genotype. The individual carried COMT met allele differed from individuals carried COMT val allele in delayed memory, WCST errors and perseverative errors. No evidence show significantly difference among DRD4exonIII48bp VNTR, DAT1, IL-lRa86bp, IL-ipexon5 gene Polymorphism and Cognitive Function. 5. Apart from anxiety, those factor score of Corners Parent Rating Scales in children with GTS were significantly different from that in healthy control group. 6. There was a significantly different effect for the number of word fluency, errors of WCST test, categories control and perseverative errors of WCST test compared with normal controls. 7. For the GTS group, Yale Tic Severity scores correlated significantly with some psychological test. [Conclusion] 1. The long repeat allele of the DRD4 48-bp repeat polymorphism was significantly associated with ADHD. This linkage showed the long repeat allele may be a risk factor for GTS+ADHD subjects. For the GTS+ADHD group, the 240bp allele of IL-IRa gene Polymorphism perhaps is another risk factor. 2. These data are consistent with the results of other studies examining the role of COMT in cognitive function. GTS subjects with the met allele produced fewer perseverative errors on the Wisconsin Card Sorting Test than subjects with the val allele, suggesting that a functional genetic polymorphism may influence prefrontal cognition.. No evidence showed the association among DRD4exonIII48bp VNTR,DAT1, IL-IRa 86bp, IL-l[3exon5 gene Polymorphism and cognitive function in children with GTS. 3. GTS patient has memory, attention and executivefunction defect, these defects may have something to do with the prefrontal dopamine disfunction. For comorbid, there is a certain influence in the cognition function. 4. GTS parents carry out function defects as the risky colony, this kind of defect may be involved in many attitudes of COMTmet/val gene polymorphism. The impact of COMTmet/val gene polymorphism on mankind's cognitive function may be commom. 5. The symptom severity of GTS may correlate with cognitive function.