title: Serotonin genes and gene-gene interactions in borderline personality disorder in a matched case-control study.
abstract: Lines of evidence suggest serotonin genes are susceptibility candidates in borderline personality disorder (BPD). However, few molecular genetic studies on BPD have been reported, especially an overall lack of study on epistatic interactions. We genotyped 27 polymorphisms in 7 serotonin genes in 113 Caucasian BPD patients and matched (sex, age and ethnicity) controls. Program UNPHASED was used to perform association analyses for genotypes, alleles and haplotypes with a permutation test of 10,000 simulations. The Multifactor Dimensionality Reduction analysis was used to examine gene-gene interactions in serotonin system, including three other genes (5-HTT, 5-HT2A and MAOA) that we previously reported. Genotype and allele analyses showed that BPD significantly associated with 5-HT2C and TPH2. BPD patients had high frequencies of the 5-HT2C rs6318G allele (p=0.021) and G/G genotype (OR=2.25); and TPH2 rs2171363T allele (p=0.001) and T containing genotypes (OR=3.40). The 5-HT1A, 5-HT1B, 5-HT1D, 5-HT3A and TPH1 showed no significant association with BPD for genotype, allele and haplotype analyses. We also detected significant interactions between 5-HT2C and TPH2 (p=0.001), and among 5-HT2C, 5-HTT, MAOA and TPH2 (p=0.001) in BPD. Patients with 5-HT2C rs6318G/G genotype had a high frequency of TPH2 rs2171363C/T genotype compared with controls. Our study indicates ""that serotonin genes and their interactions may play a role in the susceptibility to borderline personality disorder.
authors.affiliation: Neurogenetics Section, Centre for Addiction and Mental Health (CAMH), 250 College Street, Toronto, Canada M5T1R8. xingqunni@hotmail.com
authors.forename: Xingqun
authors.initials: X
authors.lastname: Ni
authors.forename: David
authors.initials: D
authors.lastname: Chan
authors.forename: Kirsten
authors.initials: K
authors.lastname: Chan
authors.forename: Shelley
authors.initials: S
authors.lastname: McMain
authors.forename: James L
authors.initials: JL
authors.lastname: Kennedy
mesh_terms: D000328:Adult; D001883:Borderline Personality Disorder / Q000235:genetics*; D016022:Case-Control Studies; D004843:Epistasis, Genetic; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008995:Monoamine Oxidase / Q000235:genetics; D011110:Polymorphism, Genetic; D011985:Receptors, Serotonin / Q000235:genetics; D012701:Serotonin / Q000235:genetics*; D014365:Tryptophan Hydroxylase / Q000235:genetics
chemical_list: D011985:Receptors, Serotonin; D012701:Serotonin; D014365:Tryptophan Hydroxylase; D008995:Monoamine Oxidase