Association of Smoking Behavior with an Odorant Receptor Allele Telomeric to the Human Major Histocompatibility Complex
- 1 December 2008
- journal article
- research article
- Published by Mary Ann Liebert Inc in Genetic Testing
- Vol. 12 (4), 481-486
- https://doi.org/10.1089/gte.2008.0029
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.Keywords
This publication has 42 references indexed in Scilit:
- Structural determinants of odorant recognition by the human olfactory receptors OR1A1 and OR1A2Journal of Structural Biology, 2007
- Smoking is a risk factor for multiple sclerosis: a metanalysisMultiple Sclerosis Journal, 2007
- A high-resolution HLA and SNP haplotype map for disease association studies in the extended human MHCNature Genetics, 2006
- Rheumatoid arthritis etiology and HLA‐linked odorant receptor gene polymorphisms: Comment on the article by Klareskog et alArthritis & Rheumatism, 2006
- The Haplotype Structure of the Human Major Histocompatibility ComplexHuman Immunology, 2006
- A new model for an etiology of rheumatoid arthritis: Smoking may trigger HLA–DR (shared epitope)–restricted immune reactions to autoantigens modified by citrullinationArthritis & Rheumatism, 2005
- Gene map of the extended human MHCNature Reviews Genetics, 2004
- Haploview: analysis and visualization of LD and haplotype mapsBioinformatics, 2004
- Why people smokeBMJ, 2004
- Relationship of tridimensional personality questionnaire scores and smoking variables in female and male smokersJournal of Substance Abuse, 1992