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

Authors
Santos, Pablo Sandro Carvalho; Füst, George; Prohászka, Zoltán; Volz, Armin; Horton, Roger; Miretti, Marcos Mateo; Yu, Chack-Yung; Beck, Stephan G.; Uchanska-Ziegler, Barbara; Ziegler, Andreas
Publication Year
2008
Language
English
Format
article
Status
Published version
Description
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. © Copyright 2008, Mary Ann Liebert, Inc. 2008.
Fil: Santos, Pablo Sandro Carvalho. Charité – Universitätsmedizin Berlin;
Fil: Füst, George. Semmelweis Egyetem;
Fil: Prohászka, Zoltán. Magyar Tudomanyos Akademia; . Semmelweis Egyetem;
Fil: Volz, Armin. Charité – Universitätsmedizin Berlin;
Fil: Horton, Roger. Wellcome Trust Sanger Institute;
Fil: Miretti, Marcos Mateo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Universidad Nacional de Misiones. Instituto de Biología Subtropical; Argentina. Wellcome Trust Sanger Institute;
Fil: Yu, Chack-Yung. Ohio State University; Estados Unidos
Fil: Beck, Stephan G.. Ucl Cancer Institute;
Fil: Uchanska-Ziegler, Barbara. Charité – Universitätsmedizin Berlin;
Fil: Ziegler, Andreas. Charité – Universitätsmedizin Berlin;
Subject
HLA haplotype
Smoking
Otras Ciencias Biológicas
Ciencias Biológicas
CIENCIAS NATURALES Y EXACTAS
Access level
Restricted access
License
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/60931