圖片來源：medicalxpress.com
近日，一項刊登在國際雜誌Translational Psychiatry上的研究報告中，來自赫爾辛基大學的科學家通過研究發現了一種遺傳突變，該突變可是的攜帶者喝醉酒後出現特別衝動和魯莽的行為，研究者指出，在芬蘭超過10萬人都攜帶這種突變。
許多芬蘭人都知道有些人喝醉後會行為會變得過度奇怪且不穩定，文章中研究者推測這或許是某些生物因素所導致的；研究者Roope Tikkanen博士表示，如今我們發現血清素2B受體基因的點圖片或許會使得攜帶者更加易於出現衝動行為，尤其是在酒後表現尤為明顯，這項研究是對2010年發表在Nature雜誌上的研究結果的補充，Nature雜誌上研究者Bevilacqua闡述了在芬蘭人機體中發現了血清素2B受體的突變。
本文研究結果表明，攜帶該突變的個體在自然狀態下易於變得衝動，而且這些個體非常有可能掙紮於自我控製和情緒障礙中；目前研究者對血清素2B受體在人類機體中的功能知之甚少，但其被認為和個體情緒衝動相關，盡管這隻是在很少一部分人中出現的精神健康問題，本文中研究者在2.2%的人群中發現了該基因的突變，一個基因在複雜現象中的影響往往是次要的，但其卻有可能幫助鑒別出該基因對人群的影響，比如基因突變對芬蘭人的影響等。
如果這些研究結果在遭受衝動控製困難的單一個體的大量臨床樣本中表現較為明顯，那麼研究者或許就可以采取一定的保護措施，而最為重要的措施明顯就是控製個體的酒精消耗，其它的措施還包括嚐試通過認知行為精神療法和藥物療法來對個體的行為進行控製。除了芬蘭人群體健康的假定影響外，本文研究發現還揭示了血清素2B受體在人類機體中的重要角色，研究者還需要進行更多研究來揭示該基因表達的影響，即基因表達的蛋白產物可以在多種方式中受到影響。
最後研究者表示，本文研究闡明了血清素2B受體在個體健康中的影響，而增加對血清素2B受體功能的理解對於後期開發新型藥理學方法來治療相關疾病的患者提供了一定的幫助和思路。
doi:10.1038/tp.2015.170
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Impulsive alcohol-related risk-behavior and emotional dysregulation among individuals with a serotonin 2B receptor stop codon
R Tikkanen1,2, J Tiihonen3,4,5, M R Rautiainen5, T Paunio1,5,6, L Bevilacqua7, R Panarsky8, D Goldman8 and M Virkkunen1,6
A relatively common stop codon (Q20*) was identified intheserotonin 2B receptor gene (HTR2B) in a Finnish founder population in 2010 and it was associated with impulsivity. Here we examine the phenotype of HTR2B Q20* carriers in a setting comprising 14 heterozygous HTR2B Q20* carriers and 156 healthy controls without the HTR2B Q20*. The tridimensional personality questionnaire, Brown–Goodwin lifetime aggression scale, the Michigan alcoholism screening test and lifetime drinking history were used to measure personality traits, impulsive and aggressive behavior, both while sober and under the influence of alcohol, and alcohol consumption.Regressionanalyses showed that among the HTR2B Q20* carriers, temperamental traits resembled a passive-dependent personality profile, and the presence of the HTR2B Q20* predicted impulsive and aggressive behaviors particularly under the influence of alcohol. Results present examples of how one gene may contribute to personality structure and behaviors in a founder population and how personality may translate into behavior.
doi:10.1038/nature09629
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A population-specific HTR2B stop codon predisposes to severe impulsivity
Laura Bevilacqua, Stéphane Doly, Jaakko Kaprio, Qiaoping Yuan, Roope Tikkanen, Tiina Paunio, Zhifeng Zhou, Juho Wedenoja, Luc Maroteaux, Silvina Diaz, Arnaud Belmer, Colin A. Hodgkinson, Liliana Dell’Osso, Jaana Suvisaari, Emil Coccaro, Richard J. Rose, Leena Peltonen, Matti Virkkunen &David Goldman
Impulsivity, describing action without foresight, is an important feature of several psychiatric diseases, suicidality and violent behaviour. The complex origins of impulsivity hinder identification of the genes influencing it and the diseases with which it is associated. Here we perform exon-focused sequencing of impulsive individuals in a founder population, targeting fourteen genes belonging to the serotonin and dopamine domain. A stop codon in HTR2B was identified that is common (minor allele frequency > 1%) but exclusive to Finnish people. Expression of the gene in the human brain was assessed, as well as the molecular functionality of the stop codon, which was associated with psychiatric diseases marked by impulsivity in both population and family-based analyses. Knockout of Htr2b increased impulsive behaviours in mice, indicative of predictive validity. Our study shows the potential for identifying and tracing effects of rare alleles in complex behavioural phenotypes using founder populations, and indicates a role for HTR2B in impulsivity.
