Genetic basis of tobacco smoking: strong association of a specific major histocompatibility complex haplotype on chromosome 6 with smoking behavior.

2.50
Hdl Handle:
http://hdl.handle.net/2336/65220
Title:
Genetic basis of tobacco smoking: strong association of a specific major histocompatibility complex haplotype on chromosome 6 with smoking behavior.
Authors:
Füst, George; Arason, Gudmundur J; Kramer, Judith; Szalai, Csaba; Duba, Jeno; Yang, Yan; Chung, Erwin K; Zhou, Bi; Blanchong, Carol A; Lokki, Marja-Liisa; Bodvarsson, Sigurdur; Prohászka, Zoltán; Karádi, István; Vatay, Agnes; Kovács, Margit; Romics, László; Thorgeirsson, Gudmundur; Yu, C Yung
Citation:
Int. Immunol. 2004, 16(10):1507-14
Issue Date:
1-Oct-2004
Abstract:
The genetic basis for addiction to tobacco smoking--particularly that of the perception of olfactory stimuli that may be important in reinforcing smoking addiction--is largely unknown. A cluster of genes for olfactory receptors is in close proximity to the MHC region on chromosome 6. Polymorphisms of MHC class III genes (RCCX modules, TNFA promoter polymorphisms) were determined in 101 healthy subjects and 232 coronary artery disease (CAD) patients from Hungary with defined tobacco smoking habits. A highly significant association between ever smoking (past + current smokers) and a specific MHC haplotype was observed (odds ratios = 2.14-4.13; P-values = 0.012 to <0.001). This haplotype is characterized by the presence of C4A null alleles and a solitary short C4B gene linked to the TNF2 allele of the promoter for TNFA gene. This haplotype occurred more frequently in the ever smokers than in the never smokers [odds ratio: 4.97 (1.96-12.62); P = 0.001], and such associations were stronger in women (odds ratio = 13.6) than in men (odds ratio = 2.79). An independent study of complement C4 protein polymorphism and smoking habits in Icelandic subjects (n = 351) yielded similar and confirmative results. Considering the documented link between olfactory stimuli and smoking in females, and the presence of a cluster of odorant receptor genes close to the MHC class I region, our findings implicate a potential role of the MHC-linked olfactory receptor genes in the initiation of smoking.
Description:
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field
Additional Links:
http://intimm.oxfordjournals.org/cgi/content/abstract/16/10/1507

Full metadata record

DC FieldValue Language
dc.contributor.authorFüst, George-
dc.contributor.authorArason, Gudmundur J-
dc.contributor.authorKramer, Judith-
dc.contributor.authorSzalai, Csaba-
dc.contributor.authorDuba, Jeno-
dc.contributor.authorYang, Yan-
dc.contributor.authorChung, Erwin K-
dc.contributor.authorZhou, Bi-
dc.contributor.authorBlanchong, Carol A-
dc.contributor.authorLokki, Marja-Liisa-
dc.contributor.authorBodvarsson, Sigurdur-
dc.contributor.authorProhászka, Zoltán-
dc.contributor.authorKarádi, István-
dc.contributor.authorVatay, Agnes-
dc.contributor.authorKovács, Margit-
dc.contributor.authorRomics, László-
dc.contributor.authorThorgeirsson, Gudmundur-
dc.contributor.authorYu, C Yung-
dc.date.accessioned2009-04-17T09:32:07Z-
dc.date.available2009-04-17T09:32:07Z-
dc.date.issued2004-10-01-
dc.date.submitted2009-04-17-
dc.identifier.citationInt. Immunol. 2004, 16(10):1507-14en
dc.identifier.issn0953-8178-
dc.identifier.pmid15339882-
dc.identifier.doi10.1093/intimm/dxh152-
dc.identifier.urihttp://hdl.handle.net/2336/65220-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractThe genetic basis for addiction to tobacco smoking--particularly that of the perception of olfactory stimuli that may be important in reinforcing smoking addiction--is largely unknown. A cluster of genes for olfactory receptors is in close proximity to the MHC region on chromosome 6. Polymorphisms of MHC class III genes (RCCX modules, TNFA promoter polymorphisms) were determined in 101 healthy subjects and 232 coronary artery disease (CAD) patients from Hungary with defined tobacco smoking habits. A highly significant association between ever smoking (past + current smokers) and a specific MHC haplotype was observed (odds ratios = 2.14-4.13; P-values = 0.012 to <0.001). This haplotype is characterized by the presence of C4A null alleles and a solitary short C4B gene linked to the TNF2 allele of the promoter for TNFA gene. This haplotype occurred more frequently in the ever smokers than in the never smokers [odds ratio: 4.97 (1.96-12.62); P = 0.001], and such associations were stronger in women (odds ratio = 13.6) than in men (odds ratio = 2.79). An independent study of complement C4 protein polymorphism and smoking habits in Icelandic subjects (n = 351) yielded similar and confirmative results. Considering the documented link between olfactory stimuli and smoking in females, and the presence of a cluster of odorant receptor genes close to the MHC class I region, our findings implicate a potential role of the MHC-linked olfactory receptor genes in the initiation of smoking.en
dc.language.isoenen
dc.publisherOxford University Pressen
dc.relation.urlhttp://intimm.oxfordjournals.org/cgi/content/abstract/16/10/1507en
dc.subject.meshAdulten
dc.subject.meshBlotting, Southernen
dc.subject.meshChromosomes, Human, Pair 6en
dc.subject.meshComplement C4aen
dc.subject.meshComplement C4ben
dc.subject.meshCoronary Artery Diseaseen
dc.subject.meshFemaleen
dc.subject.meshGenetic Predisposition to Diseaseen
dc.subject.meshHaplotypesen
dc.subject.meshHistocompatibility Antigensen
dc.subject.meshHumansen
dc.subject.meshHungaryen
dc.subject.meshIcelanden
dc.subject.meshMaleen
dc.subject.meshMiddle Ageden
dc.subject.meshPolymorphism, Single Nucleotideen
dc.subject.meshReceptors, Odoranten
dc.subject.meshSex Factorsen
dc.subject.meshSmokingen
dc.subject.meshTumor Necrosis Factor-alphaen
dc.titleGenetic basis of tobacco smoking: strong association of a specific major histocompatibility complex haplotype on chromosome 6 with smoking behavior.en
dc.typeArticleen
dc.contributor.departmentThird Department of Internal Medicine, Semmelweis University and Hungarian Academy of Sciences, Budapest, Hungary. FustGe@kut.sote.huen
dc.identifier.journalInternational immunologyen

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