GENETIC STUDY: Association between the BclI glucocorticoid receptor polymorphism and smoking in a sample of patients with obstructive airway disease

Abstract

Glucocorticoids seem to mediate the effect of stimulant drugs such as nicotine. Several studies have pointed to an association between the BclI polymorphism in the glucocorticoid receptor gene and increased glucocorticoid effects. We analysed the association of smoking behaviour and the BclI polymorphism using a case-control design within the framework of a larger pharmacogenetic study. A total of 327 Caucasian patients with asthma or chronic obstructive pulmonary disease from 39 German general practices gave informed consent to take part in the study. They filled in questionnaires concerning their smoking behaviour and were genotyped for the BclI polymorphism. The genotype frequencies for non-smokers (n = 251; CC, 0.42; CG, 0.46; GG, 0.12) as well as for smokers (n = 76; CC, 0.29; CG, 0.55; GG, 0.16) were consistent with the Hardy-Weinberg equilibrium. The proportion of smokers was significantly lower among carriers of the CC-genotype (22/127 = 17%) compared with carriers of the G-allele (54/200 = 27%; chi2 = 4.08; P = 0.04). Within the group of smokers, the proportion of heavy smokers (> 19 cigarettes/day; median) was reduced in C-homozygous patients when compared with carriers of the G-allele (7/22 = 32% versus 31/54 = 57%; chi2 = 4.09; P = 0.04). Stepwise logistic regression analysis also pointed to an association between the CC-genotype and a reduced probability of being a smoker (odds ratio = 0.55; 95% confidence interval = 0.30-1.00; P = 0.05) controlling for other predictors. In summary, this study provides evidence that the BclI polymorphism might play a role in the maintenance and severity of nicotine dependence.

Examining sex differences in pleiotropic effects for depression and smoking using polygenic and gene‐region aggregation techniques

“…In contrast to previous research (e.g., Rogausch et al, 2007;Tang et al, 2015), genetic variation within the NR3C1 and CRHR1…”

“…Gillespie, Phifer, Bradley, & Ressler, 2009), only a handful of studies have examined associations with smoking behavior. For example, Rogausch, Kochen, Meineke, and Hennig (2007) found that G allele carriers at rs41423247 of NR3C1 were more likely to become smokers and had significantly higher daily cigarette consumption than C homozygotes. Other SNPs within NR3C2, FKBP5, and CRHR1 have also been examined in relation to smoking outcomes (dos Santos et al, 2012;Jensen et al, 2015;Koopmann et al, 2016;Rovaris et al, 2013;Tang et al, 2015), with mixed results.…”

Cohort Profile: Sympathetic activity and Ambulatory Blood Pressure in Africans (SABPA) prospective cohort study

“…11 Power analyses were therefore performed for the SABPA study cohort. Using previous studies, ambulatory autonomic dysfunction 12 and cortisol data 13 , 14 were used to obtain relevant effect sizes based on differences in biological profiles and genotyping hypothalamic-pituitary-adrenal (HPA) axis variation. Resulting sample sizes of 50–416 would enable explanation of biological differences and detection of single nucleotide polymorphisms (SNPs) with a statistical power of 0.8, and level of significance of 0.05.…”

Genome-Wide Association Study of Smoking Behavior Traits in a Chinese Han Population

“…A further investigation using the PROMO prediction tool (30) suggested that the locus of rs139753473 interacted with two transcription factors, including the glucocorticoid receptor alpha and the androgen receptor. Interestingly, the glucocorticoid receptor has been reported to be associated with the probability of smoking severity and cessation in a sample of obstructive airway disease patients (31). It has been suggested that cigarette smoking could increase androgen receptor activity (32).…”