Elia Josephine, Devoto Marcella
The Children's Hospital of Philadelphia, Science Center, 3440 Market Street, Philadelphia, PA 19104-6209, USA.
Curr Psychiatry Rep. 2007 Oct;9(5):434-9. doi: 10.1007/s11920-007-0057-z.
Attention-deficit/hyperactivity disorder (ADHD) is highly heritable. Confirmed association has been reported for several candidate genes, including DAT1, DRD4, SNAP-25, DRD5, 5HTT, HTR1B, and DBH; however, these confer relatively small risk. Family-based linkage studies have identified a number of chromosomal regions containing potential ADHD predisposing loci, some overlapping in two or more studies, including 5p, 6q, 7p, 11q, 12q, and 17p. New large-scale studies that apply recent technological advances to perform high-density genotyping of the entire genome, in combination with information on the haplotype structure of the human genome, now allow testing of single-nucleotide polymorphism association with disease phenotype without any a priori hypothesis. They may contribute further to our understanding of the genetic factors involved in ADHD. The heterogeneous complex ADHD phenotype, as well as epigenetic factors may be contributing to the challenge of genetic studies. Samples that include limited age ranges may have better success at uncovering genes whose expression is limited to specific developmental stages.
注意缺陷多动障碍（ADHD）具有高度遗传性。已报道多个候选基因存在确切关联，包括多巴胺转运体1（DAT1）、多巴胺受体D4（DRD4）、突触小体相关蛋白25（SNAP - 25）、多巴胺受体D5（DRD5）、5 - 羟色胺转运体（5HTT）、5 - 羟色胺受体1B（HTR1B）和多巴胺β-羟化酶（DBH）；然而，这些基因带来的风险相对较小。基于家系的连锁研究已确定了多个包含潜在ADHD易感位点的染色体区域，其中一些在两项或更多研究中存在重叠，包括5号染色体短臂（5p）、6号染色体长臂（6q）、7号染色体短臂（7p）、11号染色体长臂（11q）、12号染色体长臂（12q）和17号染色体短臂（17p）。如今，新的大规模研究应用最新技术进展对整个基因组进行高密度基因分型，并结合人类基因组单倍型结构信息，从而能够在没有任何先验假设的情况下检测单核苷酸多态性与疾病表型的关联。这些研究可能会进一步增进我们对ADHD相关遗传因素的理解。ADHD复杂的异质性表型以及表观遗传因素可能是遗传研究面临挑战的原因。纳入年龄范围有限的样本在发现那些表达仅限于特定发育阶段的基因方面可能会更成功。
