Abstract
Cigarette smoking is a complex behavioral phenotype to which environmental, psychological and genetic factors contribute. The purpose of this study was to investigate these multifactorial effects with a specific focus on young women and on genes that encode serotonin (5-HT) receptors and the 5-HT transporter. A case–control sample of female Israeli college students provided comprehensive background data and details of cigarette smoking and completed a battery of psychological instruments. They were divided into smoking initiators (SI, n=242) or non-initiators (NI, n=148); SI were further subdivided into high (HND, n=127) and low nicotine-dependent smokers (LND, n=115) on the basis of their scores on the Fagerstrom Tolerance Questionnaire (FTQ). Single-nucleotide polymorphisms (SNPs) in five serotonin receptor genes (HTR1A, HTR1B, HTR2A, HTR2C and HTR6) and the 5-HT transporter-linked polymorphic region (5-HTTLPR) were genotyped. In a logistic regression model for SI (χ2=117.90, P=1.6 × 10−19, Nagelkerke R2=0.42), novelty seeking (odds ratio (OR)=1.134, P=0.00009) was a significant risk factor. A five SNP CACCC haplotype in HTR6 was a strong protective factor against SI (OR=0.26; P=0.007). The interaction of HTR6-C276T genotype and lifetime traumatic experience contributed strongly to the risk of SI (OR=13.88, P=0.0001). Specifically, subjects homozygous for the HTR6-C276T C allele showed significantly increased risk of SI if they had experienced trauma. Although significant (χ2=42.85, P=1.00 × 10−7), the best-fitting model for ND was less predictive than the model for SI (Nagelkerke R2=0.24). HTR1B-G861C GG genotype (OR=2.29, P=0.01) was a significant risk factor for HND. Further studies should consider the interactive contribution of life events and relevant gene variants to cigarette smoking and other complex behavioral traits.
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Acknowledgements
Research described in this article was supported in part by Philip Morris USA Inc. and Philip Morris International. The project was initiated by the investigators and the sponsor had no role in its design, in the analysis and interpretation of the data or in the preparation of the paper. We thank Inge Gritsenko for excellent technical assistance.
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Lerer, E., Kanyas, K., Karni, O. et al. Why do young women smoke? II. Role of traumatic life experience, psychological characteristics and serotonergic genes. Mol Psychiatry 11, 771–781 (2006). https://doi.org/10.1038/sj.mp.4001855
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DOI: https://doi.org/10.1038/sj.mp.4001855
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