近日,，來(lái)自美國(guó)華盛頓大學(xué)的研究者研究指出，導(dǎo)致戒煙很困難的基因變異可以增加重度吸煙者對(duì)于尼古丁替代療法或者藥物的反應(yīng),。相關(guān)研究于5月30日刊登在了國(guó)際雜志Journal of Psychiatry上,。這項(xiàng)研究指出,，未來(lái)我們有可能預(yù)測(cè)病人通過(guò)尼古丁成癮療法藥物治療所帶來(lái)的好處,。
吸煙者的遺傳基因組成使其處于一種重度沉迷抽煙的風(fēng)險(xiǎn)之中,，這項(xiàng)研究中，研究者分析了來(lái)自社區(qū)的5000名參與者和來(lái)自臨床治療的1000名參與者的數(shù)據(jù)，研究者研究了他們成功戒煙的能力和遺傳變異之間的關(guān)系,，而且這也和重度吸煙以及尼古丁依賴風(fēng)險(xiǎn)之間有一定聯(lián)系,。
高危基因標(biāo)記的人相比沒(méi)有標(biāo)記的人平均多吸兩年時(shí)間的煙,，他們通過(guò)藥物治療戒煙的可能性更小一些,。相同的基因變異可以預(yù)測(cè)一個(gè)人對(duì)于戒煙療法的效應(yīng)，而且那些高?；驑?biāo)記的人更容易對(duì)藥物療法產(chǎn)生反應(yīng),。在臨床試驗(yàn)中，高危個(gè)體對(duì)于藥物治療（如尼古丁貼劑）的反應(yīng)比一般個(gè)體高出三倍,；而且抗抑郁藥物安非他酮可以幫助患者戒煙,。
研究者Bierut和Chen表示，基因的變異涉及到一個(gè)人是否吸煙,，變得對(duì)尼古丁沉迷,，難以戒掉,。研究者們表示相同的基因可以預(yù)測(cè)重度吸煙者以及其對(duì)于藥物治療的反應(yīng),，遺傳變異對(duì)于解開(kāi)成癮之謎至關(guān)重要。
研究者Bierut表示,，這就好比是一個(gè)“棱角”（corner piece）而已,，而且是解開(kāi)這個(gè)謎底的重要的一部分，涉及到變異的這些基因固然重要,，但是其它的基因和環(huán)境因素也扮演著重要角色,。目前研究者已經(jīng)鑒定出了對(duì)于藥物治療有反應(yīng)的一組以及沒(méi)有任何反應(yīng)的一組，這將對(duì)于幫助人們成功戒煙至關(guān)重要,。
沒(méi)有遺傳變異風(fēng)險(xiǎn)的人群并不會(huì)對(duì)藥物產(chǎn)生反應(yīng),，這些人群應(yīng)當(dāng)通過(guò)咨詢或者非藥物治療手段來(lái)進(jìn)行治療。研究者Chen表示,，這項(xiàng)研究將拉近我們和個(gè)體化用藥的距離,，盡管早期研究揭示了基因?qū)τ诔闊熀统砂a有適度的影響。新的臨床發(fā)現(xiàn)揭示了遺傳變異對(duì)于吸煙者治療效應(yīng)有重要的效應(yīng)及影響,。（生物谷Bioon.com）
doi:10.1176/appi.ajp.2012.11101545
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PMID:
Interplay of Genetic Risk Factors (CHRNA5-CHRNA3-CHRNB4) and Cessation Treatments in Smoking Cessation Success
Li-Shiun Chen, M.D., M.P.H., Sc.D.; Timothy B. Baker, Ph.D.; Megan E. Piper, Ph.D.; Naomi Breslau, Ph.D.; Dale S. Cannon, Ph.D.; Kimberly F. Doheny, Ph.D.; Stephanie M. Gogarten, Ph.D.; Eric O. Johnson, Ph.D.; Nancy L. Saccone, Ph.D.; Jen C. Wang, Ph.D.; Robert B. Weiss, Ph.D.; Alison M. Goate, D.Phil.; Laura Jean Bierut, M.D.
Objective: Smoking is highly intractable, and the genetic influences on cessation are unclear. Identifying the genetic factors affecting smoking cessation could elucidate the nature of tobacco dependence, enhance risk assessment, and support development of treatment algorithms. This study tested whether variants in the nicotinic receptor gene cluster CHRNA5-CHRNA3-CHRNB4 predict age at smoking cessation and relapse after an attempt to quit smoking. Method: In a community-based, cross-sectional study (N=5,216) and a randomized comparative effectiveness smoking cessation trial (N=1,073), the authors used Cox proportional hazard models and logistic regression to model the relationships of smoking cessation (self-reported quit age in the community study and point-prevalence abstinence at the end of treatment in the clinical trial) to three common haplotypes in the CHRNA5-CHRNA3-CHRNB4 region defined by rs16969968 and rs680244. Results: The genetic variants in the CHRNA5-CHRNA3-CHRNB4 region that predict nicotine dependence also predicted a later age at smoking cessation in the community sample. In the smoking cessation trial, haplotype predicted abstinence at end of treatment in individuals receiving placebo but not among individuals receiving active medication. Haplotype interacted with treatment in affecting cessation success. Conclusions: Smokers with the high-risk haplotype were three times as likely to respond to pharmacologic cessation treatments as were smokers with the low-risk haplotype. The high-risk haplotype increased the risk of cessation failure, and this increased risk was ameliorated by cessation pharmacotherapy. By identifying a high-risk genetic group with heightened response to smoking cessation pharmacotherapy, this work may support the development of personalized cessation treatments.
