The association between CHRN genetic variants and dizziness at first inhalation of cigarette smoke

Abstract

Numerous single nucleotide polymorphisms (SNPs) in multiple nicotinic receptor genes (CHRN) are associated with smoking. However few studies have examined the association between CHRN SNPs and subjective responses to smoking in adolescents which may relate to sustained smoking, such as dizziness at first inhalation. The objective of this study was to investigate the association between 61 SNPs in eight CHRN genes (CHRNA3, CHRNA4, CHRNA5, CHRNA6, CHRNA7, CHRNB2, CHRNB3, CHRNB4) and dizziness at first inhalation. Data were available from a longitudinal cohort investigation of 1293 students 12-13year-old at baseline. Students completed self-report questionnaires at school every 3months for 5years during secondary school, and a mailed questionnaire three years later. DNA extracted from blood or saliva was genotyped for 61 CHRN SNPs selected using a gene tagging approach. Associations were modeled using logistic regression controlling for sex, race and age at first cigarette. Complete data were available for 356 of 475 participants (75%) who initiated smoking. The minor alleles of three SNPs in CHRNA6 (rs7812298, rs2304297, rs7828365) were associated with a decreased probability of dizziness (OR(95% CI)=0.54 (0.36, 0.81), 0.59 (0.40, 0.86) and 0.58 (0.36, 0.95), respectively), while one SNP in each of three other genes (rs3743077 (CHRNA3), rs755204 (CHRNA4), rs7178176 (CHRNA7)) was associated with an increased probability of dizziness (OR(95% CI)=1.40 (1.02, 1.90), 1.85 (1.05, 3.27) and 1.51 (1.06, 2.15), respectively). Thus, several SNPs located in CHRN genes are associated with dizziness at first inhalation, a smoking initiation phenotype that may relate to sustained smoking.

Keywords: Adolescent; Cigarette initiation; Genetic association; Nicotine; Nicotinic cholinergic receptors; SNP.