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Association of smoking behavior with an odorant receptor allele telomeric to the human major histocompatibility complex

Sandro Carvalho Santos, P.; Füst, G.; Prohászka, Z.; Volz, A.; Horton, R.; Miretti, M.; Yu, C.-Y.; ... Ziegler, A.; + view all (2008) Association of smoking behavior with an odorant receptor allele telomeric to the human major histocompatibility complex. Genetic Testing , 12 (4) pp. 481-486. 10.1089/gte.2008.0029. Green open access

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Abstract

Smoking behavior has been associated in two independent European cohorts with the most common Caucasian human leukocyte antigen (HLA) haplotype (A1-B8-DR3). We aimed to test whether polymorphic members of the two odorant receptor (OR) clusters within the extended HLA complex might be responsible for the observed association, by genotyping a cohort of Hungarian women in which the mentioned association had been found. One hundred and eighty HLA haplotypes from Centre d'Etude du Polymorphisme Humain families were analyzed in silico to identify single-nucleotide polymorphisms (SNPs) within OR genes that are in linkage disequilibrium with the A1-B8-DR3 haplotype, as well as with two other haplotypes indirectly linked to smoking behavior. A nonsynonymous SNP within the OR12D3 gene (rs3749971T) was found to be linked to the A1-B8-DR3 haplotype. This polymorphism leads to a 97Thr → Ile exchange that affects a putative ligand binding region of the OR12D3 protein. Smoking was found to be associated in the Hungarian cohort with the rs3749971T allele (p = 1.05 × 10−2), with higher significance than with A1-B8-DR3 (p = 2.38 × 10−2). Our results link smoking to a distinct OR allele, and demonstrate that the rs3749971T polymorphism is associated with the HLA haplotype–dependent differential recognition of cigarette smoke components, at least among Caucasian women.

Type: Article
Title: Association of smoking behavior with an odorant receptor allele telomeric to the human major histocompatibility complex
Open access status: An open access version is available from UCL Discovery
DOI: 10.1089/gte.2008.0029
Publisher version: http://dx.doi.org/10.1089/gte.2008.0029
Language: English
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Wolfson Inst for Biomedical Research
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
URI: https://discovery.ucl.ac.uk/id/eprint/13875
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