| Objective:We examined the associations between 16 single nucleotide polymorphisms(SNPs)and five common methylphenidate-induced side effects(decreased appetite,insomnia,irritability,stomachaches,and nightmares)in children with attention deficit hyperactivity disorder(ADHD),in order to provide possible basis for guiding clinical medication application and improving patient compliance.Methods:108 Han children who met the ADHD diagnostic criteria of The Diagnostic and Statistical Manual of Mental Disorders,Forth Edition(DSM-?)were recruited in this study and were treated with methylphenidate for 6 weeks.The symptoms and side effects were evaluated using Barkley Stimulant Side Effect Rating Scale,Attention Deficit Hyperactivity Disorder Rating Scale-IV Home Version,Clinical Diagnostic Interview Scale and the Conners Parent Symptom Questionnaire.ECG examinations were performed at baseline and the end of six-week treatment.Patients' venous blood was collected for genetic research.16 single nucleotide polymorphisms(rs5569,rs2975226,rs8028396,rs7170028,rs2651417,rs12915695,rs806368,rs2242446,rs3746544,rs1051312,rs2244613,rs2002577,rs2283265,rs2007153,rs77905,rs6277)which belong to 8 genes(SLC6A3,DRD2,DBH,SLC6A2,SNAP25,CHRNA7,CNR1,CES1)related to dopamine system,noradrenaline system,and cannabinoid system were genotyped through the Sequenom MassARRAY platform.The associations between gene polymorphisms and five side effects,including decreased appetite,insomnia,irritability,stomachaches and nightmares were analyzed respectively.Results:1.Of the 108 patients,94 were males(87.0%)and 14 were females(13.0%).The ratio of male to female was about 6.71.The age of patients was from 6 to 15 years,with an average of 9.21±1.9 years.All 17 side effects in the Barkley Stimulant Side Effect Rating Scale were observed in the study,with a total frequency of 126,and some patients experienced two or more side effects.Among the five side effects,there were 43 cases of decreased appetite(34.1%),16 cases of insomnia(12.7%),12 cases of irritability(9.5%),9 cases of stomachaches(7.0%)and 4 cases of nightmares(3.2%).2.The genotypes frequencies of five side effects at 16 SNPs were compared respectively.In the comparison of the occurrence of decreased appetite,it was found that the frequency of CNR1 gene rs806368 T/T type was higher than that of C/C type.(P<0.0167).For children experienced insomnia or not,variances were found in SLC6A3 rs2975226 and DRD2 rs2283265 genotypes frequencies(P<0.05),but no differences was observed in further pairwise comparison.Individuals homozygous for T allele in rs2283265 of DRD2 gene displayed higher frequency for irritability than T/G genotype(P<0.0167).There was a significant difference in the frequency of nightmares among the three rs7170028 genotypes of CHRNA7 gene(P<0.05),but no further information exhibited when it comes to pairwise comparison.Finally,no association between 16 SNPs and stomachaches was found.3.Multivariate Logistic regression analysis found that T/A genotype individuals of rs2975226 in SLC6A3 gene tended to develop more insomnia as a side effect when treated with methylphenidate(OR=6.1 15,95%CI=1.547?24.172).Among the three rs2283265 genotypes(DRD2 gene),the risk of irritability in T/T homozygotes was significantly higher than that in T/G individuals(OR=18.419,95%CI=1.814?186.977).However,no significant genetic variables were found in the regression equation of decreased appetite,nightmares and stomachaches.Conclusions:1.Decreased appetite and insomnia were the two most common side effects in methylphenidate treatment of ADHD in Chinese Han children in Yunnan.2.In the methylphenidate treatment of Yunnan Han children with ADHD,the occurrence of side effects including decreased appetite,insomnia and irritability may be modulated by genetic polymorphisms. |
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