Schuch Jaqueline B, Polina Evelise R, Rovaris Diego L, Kappel Djenifer B, Mota Nina R, Cupertino Renata B, Silva Katiane L, Guimarães-da-Silva Paula O, Karam Rafael G, Salgado Carlos A I, White Melanie J, Rohde Luis A, Grevet Eugenio H, Bau Claiton H D
Department of Genetics, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Adult ADHD Outpatient Clinic, Hospital de Clínicas de Porto Alegre, RS, Brazil.
J Psychiatr Res. 2016 Sep;80:73-78. doi: 10.1016/j.jpsychires.2016.06.002. Epub 2016 Jun 4.
Polymorphisms in the CHRNA5-CHRNA3-CHRNB4 gene cluster (Chr15q25) have been robustly associated with nicotine dependence, including genome-wide studies, as well as with cognitive and neuropsychological measures. In addition, cognitive processes can be influenced by nicotine use through nicotinic acetylcholine receptors (nAChRs). Here, we evaluated the effect of polymorphisms in CHRNA5-CHRNA3-CHRNB4 gene cluster and their interaction with tobacco smoking status on cognition in patients with Attention Deficit/Hyperactivity Disorder (ADHD). Eight SNPs from the CHRNA5-CHRNA3-CHRNB4 gene cluster were evaluated on a clinical sample of 403 adults with ADHD. Cognitive performance was assessed using the Wechsler Adult Intelligence Scale-Revised (WAIS-R). Analyses of covariance were used to assess the influence of single markers and their interaction with smoking status in the Vocabulary and Block Design subtests of WAIS-R. Correction for multiple comparisons was applied. Lifetime smoking was associated to Vocabulary subtest. The TT genotypes of CHRNA5 SNPs rs588765 and rs514743 showed a trend towards association with, respectively, higher and lower scores on the Vocabulary subtest. There was a significant interaction between intergenic SNP rs8023462 and smoking on Vocabulary scores. Our results are consistent with an influence of variants in the CHRNA5-CHRNA3-CHRNB4 gene cluster on cognitive measures. The overall scenario suggests a pleiotropic role of Chr15q25 nicotinic gene cluster with complex influences in ADHD, tobacco smoking and cognitive performance, characteristics that can be partially interdependent and may share underlying genetic factors.
CHRNA5-CHRNA3-CHRNB4基因簇（位于15号染色体长臂25区）中的多态性已被证实与尼古丁依赖密切相关，包括全基因组研究，以及与认知和神经心理学指标相关。此外，认知过程可通过烟碱型乙酰胆碱受体（nAChRs）受到尼古丁使用的影响。在此，我们评估了CHRNA5-CHRNA3-CHRNB4基因簇中的多态性及其与吸烟状态的相互作用对注意力缺陷多动障碍（ADHD）患者认知的影响。对403名成年ADHD患者的临床样本评估了CHRNA5-CHRNA3-CHRNB4基因簇中的8个单核苷酸多态性（SNP）。使用韦氏成人智力量表修订版（WAIS-R）评估认知表现。采用协方差分析评估WAIS-R词汇和积木设计子测验中单个标记的影响及其与吸烟状态的相互作用。应用了多重比较校正。终生吸烟与词汇子测验相关。CHRNA5 SNP rs588765和rs514743的TT基因型分别显示出与词汇子测验得分较高和较低相关的趋势。基因间SNP rs8023462与吸烟对词汇得分有显著的相互作用。我们的结果与CHRNA5-CHRNA3-CHRNB4基因簇中的变异对认知指标的影响一致。总体情况表明，15号染色体长臂25区烟碱基因簇具有多效性作用，对ADHD、吸烟和认知表现有复杂影响，这些特征可能部分相互依赖，并可能共享潜在的遗传因素。
