Kivonat:
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
(rs3749971(T)) was found to be linked to the A1-B8-DR3 haplotype. This
polymorphism leads to a (97)Thr --> 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 rs3749971(T) allele (p = 1.05 x 10(-2)), with higher
significance than with A1-B8-DR3 (p = 2.38 x 10(-2)). Our results link smoking to
a distinct OR allele, and demonstrate that the rs3749971(T) polymorphism is
associated with the HLA haplotype-dependent differential recognition of cigarette
smoke components, at least among Caucasian women.
