Weiss Lauren A, Ober Carole, Cook Edwin H
Department of Human Genetics, The University of Chicago, Chicago, IL 60637, USA.
Hum Genet. 2006 Aug;120(1):93-100. doi: 10.1007/s00439-006-0196-z. Epub 2006 May 24.
Autism affects more males than females and is associated with disturbances of the serotonin system. The integrin beta3 (ITGB3) and serotonin transporter (SLC6A4) genes were both recently identified as male quantitative trait loci (QTLs) for serotonin levels and alleles of each have been associated with autism. Here, we use publicly available genomic resources to determine whether regulation of expression level could be the mechanism behind association between serotonin level and noncoding variation in ITGB3. We also examine whether ITGB3 might interact with SLC6A4 to contribute to autism susceptibility. Using murine and human expression data, we observe that ITGB3 and SLC6A4 expression levels are correlated (0.38<r<0.78). Moreover, genetic variation in ITGB3 is associated with expression of both ITGB3 (P=0.012) and SLC6A4 (P=0.008) in unrelated CEPH individuals. We also show preliminary evidence that genotypes at the ITGB3 and SLC6A4 loci may interact to affect autism susceptibility (P=0.033).
自闭症在男性中的发病率高于女性，且与血清素系统紊乱有关。整合素β3（ITGB3）基因和血清素转运体（SLC6A4）基因最近均被确定为血清素水平的男性数量性状基因座（QTL），且每个基因的等位基因都与自闭症有关。在此，我们利用公开可用的基因组资源来确定表达水平的调控是否可能是血清素水平与ITGB3非编码变异之间关联背后的机制。我们还研究了ITGB3是否可能与SLC6A4相互作用，以增加自闭症易感性。利用小鼠和人类的表达数据，我们观察到ITGB3和SLC6A4的表达水平相关（0.38<r<0.78）。此外，在无关的CEPH个体中，ITGB3的基因变异与ITGB3（P=0.012）和SLC6A4（P=0.008）的表达均相关。我们还展示了初步证据，表明ITGB3和SLC6A4基因座的基因型可能相互作用，影响自闭症易感性（P=0.033）。
