Nakamura M, Ueno S, Sano A, Tanabe H
Department of Neuropsychiatry, Ehime University School of Medicine, Onsen-gun, Japan.
Mol Psychiatry. 1999 Mar;4(2):155-62. doi: 10.1038/sj.mp.4000515.
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.
果蝇白色基因是ATP结合盒（ABC）转运蛋白超家族的成员，参与色氨酸的细胞摄取。其人类同源基因（hW）已被定位到21号染色体的22.3区。色氨酸是神经递质血清素的前体，血清素与情绪和焦虑的调节有关。据报道，21号染色体的22.3区也与情绪障碍有关。hW基因的3'非翻译区（3'-UTR）已被证明含有一个多态性的聚（T）区域。在本研究中，我们在3'-UTR中鉴定出一个新的多态性G2457A。我们研究了这些多态性与情绪和惊恐障碍之间的关系，检测到聚（T）多态性与情绪障碍之间存在显著关联（P = 0.039（等位基因频率））。在男性中发现多态性与情绪（聚（T）多态性：P = 0.047（等位基因频率），G2457A：P = 0.040（等位基因频率），P = 0.044（基因型频率））和惊恐障碍（G2457A：P = 0.026（等位基因频率），P = 0.011（基因型频率））之间存在关联，但在女性中未发现。这些发现表明，hW基因可能是控制情绪和焦虑的重要基因，也是男性情绪障碍和惊恐障碍相关的遗传因素之一。关联的统计学显著性仍然相对较低，需要更大规模的样本进一步剖析临床表型，以证实并独立验证这一发现，并评估其意义。
