A variant associated with nicotine dependence, lung cancer and peripheral arterial disease

被引：1145

作者：

Thorgeirsson, Thorgeir E. ^{[1
]}

Geller, Frank ^{[1
]}

Sulem, Patrick ^{[1
]}

Rafnar, Thorunn ^{[1
]}

Wiste, Anna ^{[1
,2
]}

Magnusson, Kristinn P. ^{[1
]}

Manolescu, Andrei ^{[1
]}

Thorleifsson, Gudmar ^{[1
]}

Stefansson, Hreinn ^{[1
]}

Ingason, Andres ^{[1
]}

Stacey, Simon N. ^{[1
]}

Bergthorsson, Jon T. ^{[1
]}

Thorlacius, Steinunn ^{[1
]}

Gudmundsson, Julius ^{[1
]}

Jonsson, Thorlakur ^{[1
]}

Jakobsdottir, Margret ^{[1
]}

Saemundsdottir, Jona ^{[1
]}

Olafsdottir, Olof ^{[1
]}

Gudmundsson, Larus J. ^{[1
]}

Bjornsdottir, Gyda ^{[1
]}

Kristjansson, Kristleifur ^{[1
]}

Skuladottir, Halla ^{[3
]}

Isaksson, Helgi J. ^{[4
]}

Gudbjartsson, Tomas ^{[5
]}

Jones, Gregory T. ^{[8
]}

Mueller, Thomas ^{[9
]}

Gottsater, Anders ^{[10
]}

Flex, Andrea ^{[11
]}

Aben, Katja K. H. ^{[12
,13
]}

de Vegt, Femmie ^{[12
]}

Mulders, Peter F. A. ^{[14
]}

Isla, Dolores ^{[15
]}

Vidal, Maria J. ^{[15
]}

Asin, Laura ^{[16
]}

Saez, Berta ^{[17
]}

Murillo, Laura ^{[18
]}

Blondal, Thorsteinn ^{[19
]}

Kolbeinsson, Halldor ^{[6
]}

Stefansson, Jon G. ^{[6
]}

Hansdottir, Ingunn ^{[20
]}

Runarsdottir, Valgerdur ^{[20
]}

Pola, Roberto ^{[11
,21
]}

Lindblad, Bengt ^{[10
]}

van Rij, Andre M. ^{[8
]}

Dieplinger, Benjamin ^{[9
]}

Haltmayer, Meinhard ^{[9
]}

Mayordomo, Jose I. ^{[15
,16
,17
]}

Kiemeney, Lambertus A. ^{[12
,13
,14
]}

Matthiasson, Stefan E. ^{[22
]}

Oskarsson, Hogni ^{[23
]}

机构：

[1] deCODE Genet, IS-101 Reykjavik, Iceland

[2] Emory Univ, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA

[3] Landspital Univ Hosp, Dept Med Oncol, IS-101 Reykjavik, Iceland

[4] Landspital Univ Hosp, Dept Pathol, IS-101 Reykjavik, Iceland

[5] Landspital Univ Hosp, Dept Cardiothorac Surg, IS-101 Reykjavik, Iceland

[6] Landspital Univ Hosp, Dept Gen Adult Psychiat, IS-101 Reykjavik, Iceland

[7] Landspital Univ Hosp, Dept Med, IS-101 Reykjavik, Iceland

[8] Univ Otago, Dept Surg, Dunedin Sch Med, Dunedin 9054, New Zealand

[9] Konventhosp Barmherzige Brueder, Dept Lab Med, A-4020 Linz, Austria

[10] Malmo Univ Hosp, MAS, Ctr Vasc Dis, S-20502 Malmo, Sweden

[11] Univ Cattolica Sacro Cuore, Sch Med, Lab Vasc Biol & Genet, A Gemelli Univ Hosp, I-00168 Rome, Italy

[12] Radboud Univ Nijmegen Med Ctr, Dept Epidemiol & Biostat, NL-6500 HB Nijmegen, Netherlands

[13] Comprehens Canc Ctr E, NL-6501 BG Nijmegen, Netherlands

[14] Radboud Univ Nijmegen Med Ctr, Dept Urol, NL-6525 GA Nijmegen, Netherlands

[15] Univ Hosp, Div Med Oncol, Zaragoza 5009, Spain

[16] Nanotechnol Inst Aragon, Zaragoza 5009, Spain

[17] Hlth Sci Inst, Zaragoza 5009, Spain

[18] Hosp Reina Sofia, Div Med Oncol, Tudela 31500, Spain

[19] Primary Hlth Care Ctr, Dept Lung Dis, IS-101 Reykjavik, Iceland

[20] Vogur SAA Addict Treatment Ctr, IS-112 Reykjavik, Iceland

[21] IRCCS, OASI Inst Res & Care, I-94018 Troina, EN, Italy

[22] Univ Iceland, Sch Med, IS-101 Reykjavik, Iceland

[23] Therapeia, IS-101 Reykjavik, Iceland

来源：

NATURE | 2008年 / 452卷 / 7187期

关键词：

D O I：

10.1038/nature06846

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Smoking is a leading cause of preventable death, causing about 5 million premature deaths worldwide each year(1,2). Evidence for genetic influence on smoking behaviour and nicotine dependence (ND)(3-8) has prompted a search for susceptibility genes. Furthermore, assessing the impact of sequence variants on smoking-related diseases is important to public health(9,10). Smoking is the major risk factor for lung cancer (LC)(11-14) and is one of the main risk factors for peripheral arterial disease (PAD)(15-17). Here we identify a common variant in the nicotinic acetylcholine receptor gene cluster on chromosome 15q24 with an effect on smoking quantity, ND and the risk of two smoking- related diseases in populations of European descent. The variant has an effect on the number of cigarettes smoked per day in our sample of smokers. The same variant was associated with ND in a previous genomewide association study that used low- quantity smokers as controls(18,19), and with a similar approach we observe a highly significant association with ND. A comparison of cases of LC and PAD with population controls each showed that the variant confers risk of LC and PAD. The findings provide a case study of a gene - environment interaction(20), highlighting the role of nicotine addiction in the pathology of other serious diseases.

引用

页码：638 / U9

页数：5

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