Case control and family-based studies of tryptophan hydroxylase gene A218Cpolymorphism and suicidality in adolescents

The association of suicidality with polymorphism A218C in intron 7 of trypt ophan hydroxylase (TPH) gene remains controversial. The aim of this study w as to use family-based methods to examine this association in adolescents i n order to eliminate the difficulty of sampling a control group from the sa me ethnic population. Eighty-eight inpatient adolescents who recently attem pted suicide were assessed by structured interview for detailed clinical hi story, diagnoses, suicide intent, suicide risk, impulsivity, aggression, an d depression. DNA samples were collected from all subjects, from both biolo gical parents of 40 subjects and from one parent of 9 subjects; TPH allele frequencies were calculated and tested for association to phenotype, strati fied by severity, using the haplotype relative risk (HRR) and transmission disequilibrium test (TDT) methods (n = 49), The frequencies were also compa red for all the Jewish subjects (n = 84) to the known frequencies of these alleles in healthy Jewish populations. There was no significant allelic ass ociation of A218C polymorphism with suicidal behavior or other phenotypic m easures according to the HRR method (chi-square=0.094; P=0.76), the TDT (ch i-square = 0.258; P = 0.61), or association analysis to known population fr equencies (chi-square=1.667, P=0.19 for Ashkenazi, and chi-square=0.810, P= 0.37 for non-Ashkenazi), Analysis of variance with the Scheffe test demonst rated a significant difference between CC and AA genotypes in suicide risk and depression among the patients (n=88), The findings suggest that polymor phism A218C has no major relevance to the pathogenesis of adolescent suicid al behavior, but may have a subtle effect on some related phenotypes, (C) 2 001 Wiley-Liss, Inc.