POSTER NO: 355

Haplotype Analysis of the Tryptophan Hydroxylase gene, TPH, in a Slovenian Suicide Sample: a Pilot Study

¹Karen Sugden, ¹Ian W. Craig, ¹Ann Farmer, ¹Joseph McClay, ¹Peter McGuffin, ²Pat Vaughan, ¹Andrej Marusic
¹Social, Genetic and Developmental Psychiatry Research Centre, Box Number P082, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF, UK, ²HiberGen Ltd., IDA Business Centre, Bray, Co. Wicklow, Ireland

Tryptophan hydroxylase (TPH) is considered an important candidate for psychiatric and behavioural studies since it is the rate-limiting enzyme in the biosynthesis of the neurotransmitter serotonin. A number of polymorphisms have been identified within the TPH gene, promoter and surrounding region. Of these, two single nucleotide polymorphisms (SNPs) in intron 7 have been shown to be associated with both suicidal and aggressive behaviour, along with depressive and alcoholic phenotypes. It has also been demonstrated that within a sample of mentally healthy European Caucasians, the four SNPs identified within the promoter region are in complete linkage disequilibrium (LD) with each other, as are SNPs within each of introns 7, 8 and 9. One allele of an upstream microsatellite was also found to be in partial LD with the intronic SNPs. Utilization of this phenomena within the context of a haplotype provides more power to detect associations since it allows fine-scale identification of genomic areas of interest. We investigated six of the above-mentioned polymorphisms across the TPH gene region, two SNPs in the promoter, one SNP in exon 1c, one SNP in intron 7, one SNP in intron 9 and the 3' microsatellite, in a pilot study sample of Slovenian suicide completers (N=26) and matched controls. The Slovenian population has one of the highest suicide rates in Europe, whilst exhibiting, in general, a psychopathological profile of low extroversion, high neuroticism and high psychoticism. A novel allele-specific competitive assay (SNiPTAG) was employed to genotype the SNPs, which allowed pooling of the resultant PCR products and subsequent loading on a single capillary of an ABI 3100 genetic analyzer. This has the advantage of reducing both cost and workload. The resulting analyses allowed us to assess the pattern of LD between the six polymorphisms within this sample, and to investigate association between TPH gene variants and suicidal behaviour.