Polymorphisms of the human homologue of the Drosophila white gene are associated with mood and panic disorders

Abstract

The Drosophila white gene is a member of the ATP-binding cassette (ABC) transporter superfamily and is involved in the cellular uptake of tryptophan. Its human homologue gene (hW) has been mapped to chromosome 21q22.3. Tryptophan is the precursor for the neurotransmitter serotonin, which has been implicated in the regulation of mood and anxiety. The locus 21q22.3 has also been reported to be associated with mood disorders. The 3′-untranslated region (3′-UTR) in the hW gene has been shown to contain a polymorphic poly(T) region. We have identified a new polymorphism G2457A in the 3′-UTR in the present study. We examined the relationship between these polymorphisms and mood and panic disorders, and a significant association between the poly(T) polymorphisms and mood disorders was detected (P = 0.039 (allele frequency)). Associations were found between the polymorphisms and mood (poly(T) polymorphism: P = 0.047 (allele frequency), G2457A: P = 0.040 (allele frequency), P = 0.044 (genotype frequency)) and panic disorders (G2457A: P = 0.026 (allele frequency), P = 0.011 (genotype frequency)) in males, but not in females. These findings suggest that the hW gene may be an important gene in the control of mood and anxiety as well as one of the genetic factors related to mood disorders and panic disorder in males. The statistical significance of the association remains relatively low and larger materials facilitating further dissection of the clinical phenotype will be needed to confirm and independently validate this finding and to evaluate its significance.