Wassink Thomas H, Hazlett Heather C, Epping Eric A, Arndt Stephan, Dager Stephen R, Schellenberg Gerard D, Dawson Geraldine, Piven Joseph
Department of Psychiatry, The University of Iowa, USA.
Arch Gen Psychiatry. 2007 Jun;64(6):709-17. doi: 10.1001/archpsyc.64.6.709.
Autism is a heritable neurodevelopmental disorder characterized biologically by enlargement of the head and brain and abnormalities of serotonin neurotransmission.
To evaluate whether 5-HTTLPR, a functional promoter polymorphism of the serotonin transporter gene SLC6A4, influences cerebral cortical structure volumes in young male children with autism.
Association study of a genetic variant with quantitative traits.
Autism research centers at the University of North Carolina (UNC), Chapel Hill, and the University of Washington (UW), Seattle.
Forty-four male children, 2 to 4 years old, with autism participating in longitudinal brain magnetic resonance imaging studies.
Cerebral cortical and cerebellar gray and white matter volumes.
We found that 5-HTTLPR genotype influenced gray matter volumes of the cerebral cortex (F(2,23) = 7.29, P = .004) and of 3 lobe-based subregions in the UNC sample of 29 children (frontal lobe gray matter: F(2,23) = 6.36, P = .01). The 5-HTTLPR short allele appeared to be additively associated with increasing gray matter volumes, an observation affirmed by tests of linear genotype effects (cortical gray matter: F(1,24) = 14.11, P = .001; frontal lobe gray matter: F(1,24) = 13.20, P = .001). Genotype did not influence cerebellar volumes. Confirmation was pursued by means of the UW sample of 15 children. While effects were not significant in the UW sample alone, the patterns of adjusted means resembled those found in the UNC sample. Positive Cochran-Mantel-Haenszel test results supported the concordance of relationships across the 2 sites, and analyses of covariance of the combined sample that included a site covariate showed significant linear genotype effects on structure volumes (cortical gray matter: F(1,38) = 5.73, P = .02; frontal lobe gray matter: F(1,38) = 11.73, P = .002). Effect sizes of 5-HTTLPR genotype on total cortical and frontal lobe gray matter volumes were 10% and 16%, respectively.
The SLC6A4 promoter polymorphism 5-HTTLPR influences cerebral cortical gray matter volumes in young male children with autism.
自闭症是一种遗传性神经发育障碍，其生物学特征为头部和脑部增大以及血清素神经传递异常。
评估血清素转运体基因SLC6A4的功能性启动子多态性5-HTTLPR是否会影响患有自闭症的幼年男性儿童的大脑皮质结构体积。
一项关于基因变异与数量性状的关联研究。
北卡罗来纳大学教堂山分校和华盛顿大学西雅图分校的自闭症研究中心。
44名2至4岁患有自闭症的男性儿童，参与纵向脑磁共振成像研究。
大脑皮质和小脑的灰质和白质体积。
我们发现5-HTTLPR基因型影响了大脑皮质的灰质体积（F(2,23)=7.29，P=.004）以及北卡罗来纳大学29名儿童样本中3个基于脑叶的亚区域的灰质体积（额叶灰质：F(2,23)=6.36，P=.01）。5-HTTLPR短等位基因似乎与灰质体积增加呈累加关联，线性基因型效应检验证实了这一观察结果（皮质灰质：F(1,24)=14.11，P=.001；额叶灰质：F(1,24)=13.20，P=.001）。基因型并未影响小脑体积。通过华盛顿大学15名儿童的样本进行了验证。虽然单独在华盛顿大学样本中效应不显著，但调整均值的模式与在北卡罗来纳大学样本中发现的模式相似。Cochran-Mantel-Haenszel检验的阳性结果支持了两个研究地点之间关系的一致性，对包括地点协变量的合并样本进行的协方差分析显示，基因型对结构体积有显著的线性效应（皮质灰质：F(1,38)=5.73，P=.02；额叶灰质：F(1,38)=11.73，P=.002）。5-HTTLPR基因型对总皮质和额叶灰质体积的效应大小分别为10%和16%。
SLC6A4启动子多态性5-HTTLPR影响患有自闭症的幼年男性儿童的大脑皮质灰质体积。
