近日，來自美國華盛頓大學的研究者研究指出,，導致戒煙很困難的基因變異可以增加重度吸煙者對于尼古丁替代療法或者藥物的反應,。相關研究于5月30日刊登在了國際雜志Journal of Psychiatry上。這項研究指出,，未來我們有可能預測病人通過尼古丁成癮療法藥物治療所帶來的好處,。
吸煙者的遺傳基因組成使其處于一種重度沉迷抽煙的風險之中，這項研究中,，研究者分析了來自社區(qū)的5000名參與者和來自臨床治療的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系，而且這也和重度吸煙以及尼古丁依賴風險之間有一定聯(lián)系。
高?；驑擞浀娜讼啾葲]有標記的人平均多吸兩年時間的煙,，他們通過藥物治療戒煙的可能性更小一些。相同的基因變異可以預測一個人對于戒煙療法的效應,，而且那些高?；驑擞浀娜烁菀讓λ幬锆煼óa(chǎn)生反應。在臨床試驗中,，高危個體對于藥物治療（如尼古丁貼劑）的反應比一般個體高出三倍,；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人是否吸煙,，變得對尼古丁沉迷，難以戒掉,。研究者們表示相同的基因可以預測重度吸煙者以及其對于藥物治療的反應,，遺傳變異對于解開成癮之謎至關重要。
研究者Bierut表示,，這就好比是一個“棱角”（corner piece）而已,，而且是解開這個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)鑒定出了對于藥物治療有反應的一組以及沒有任何反應的一組，這將對于幫助人們成功戒煙至關重要,。
沒有遺傳變異風險的人群并不會對藥物產(chǎn)生反應，這些人群應當通過咨詢或者非藥物治療手段來進行治療,。研究者Chen表示,，這項研究將拉近我們和個體化用藥的距離，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)揭示了遺傳變異對于吸煙者治療效應有重要的效應及影響,。（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.
