Brookes Keeley J, Chen Wai, Xu Xiaohui, Taylor Eric, Asherson Philip
MRC Social Genetic Developmental Psychiatry Centre, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London, United Kingdom.
Biol Psychiatry. 2006 Nov 15;60(10):1053-61. doi: 10.1016/j.biopsych.2006.04.025. Epub 2006 Aug 7.
Fatty acids, in particular omega-3 fatty acids, have been found to affect behavior and cognition both directly and indirectly. Evidence to suggest a link with attention-deficit/hyperactivity disorder (ADHD) derives from three key areas: 1) animal dietary restriction studies observed increased locomotive hyperactivity and reduced cognitive ability in offspring; 2) animal dietary studies indicate alterations in the dopamine pathway; and 3) human studies report reduced plasma omega-3 fatty acids in ADHD subjects.
We investigated three genes that encode essential enzymes (desaturases) for the metabolism of fatty acids by scanning for genetic association between 45 single nucleotide polymorphisms (SNPs) and ADHD.
Our findings suggest a significant association of ADHD with SNP rs498793 (case-control p = .004, odds ratio [OR] 1.6, 95% confidence interval [CI] 1.15-2.23; transmission disequilibrium test [TDT] p = .014, OR 1.69) in the fatty acid desaturase 2 (FADS2) gene. As alcohol is known to decrease the activities of these desaturase enzymes, we also tested for interactions between ADHD subjects' genotypes and maternal use of alcohol during pregnancy. Two SNPs in the fatty acid desaturase 1 (FADS1) gene were nominally associated with ADHD only in the prenatal alcohol-exposed group of children; formal test for interaction was not significant.
These preliminary findings are suggestive of an association between FADS2 and ADHD.
脂肪酸,尤其是ω-3脂肪酸,已被发现可直接或间接影响行为和认知。有证据表明其与注意力缺陷多动障碍(ADHD)存在关联,这源于三个关键领域:1)动物饮食限制研究观察到后代运动性多动增加且认知能力下降;2)动物饮食研究表明多巴胺通路发生改变;3)人体研究报告ADHD受试者血浆ω-3脂肪酸水平降低。
我们通过扫描45个单核苷酸多态性(SNP)与ADHD之间的基因关联,研究了三个编码脂肪酸代谢必需酶(去饱和酶)的基因。
我们的研究结果表明,脂肪酸去饱和酶2(FADS2)基因中的SNP rs498793与ADHD存在显著关联(病例对照p = 0.004,优势比[OR] 1.6,95%置信区间[CI] 1.15 - 2.23;传递不平衡检验[TDT] p = 0.014,OR 1.69)。由于已知酒精会降低这些去饱和酶的活性,我们还测试了ADHD受试者的基因型与母亲孕期饮酒之间的相互作用。脂肪酸去饱和酶1(FADS1)基因中的两个SNP仅在产前暴露于酒精的儿童组中与ADHD存在名义上的关联;相互作用的正式检验不显著。
这些初步研究结果提示FADS2与ADHD之间存在关联。