Why do young women smoke? II. Role of traumatic life experience, psychological characteristics and serotonergic genes.
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 (chi2=117.90, P=1.6 x 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 (chi2=42.85, P=1.00 x 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.
Lerer
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E
Research Laboratory, Sara Herzog Memorial Hospital, Jerusalem, Israel. lerer@cc.huji.ac.il
Kanyas
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K
Karni
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Ebstein
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RP
Lerer
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B
D000328:Adult; D016022:Case-Control Studies; D005260:Female; D006239:Haplotypes; D006801:Humans; D007557:Israel / Q000453:epidemiology; D008016:Life Change Events; D016015:Logistic Models; D010551:Personality; D020641:Polymorphism, Single Nucleotide; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics; D044302:Receptor, Serotonin, 5-HT1B / Q000235:genetics; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics; D011985:Receptors, Serotonin / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology*
C470302:HTR1B protein, human; D044302:Receptor, Serotonin, 5-HT1B; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; C097216:serotonin 6 receptor; D044282:Receptor, Serotonin, 5-HT1A