Authors: Diego L Rovaris Nina R Mota Lucas A de Azeredo Renata B Cupertino Guilherme P Bertuzzi Evelise R Polina Verônica Contini Gustavo L Kortmann Eduardo S Vitola Eugenio H Grevet Rodrigo GrassiOliveira Sidia M CallegariJacques Claiton H D Bau
Publish Date: 2013/03/31
Volume: 120, Issue: 10, Pages: 1499-1505
Abstract
A number of studies have demonstrated that stress is involved in all aspects of smoking behavior including initiation maintenance and relapse The mineralocorticoid MR and glucocorticoid GR receptors are expressed in several brain areas and play a key role in negative feedback of the hypothalamic–pituitary–adrenal HPA axis As nicotine increases the activation of the HPA axis we wondered if functional SNPs single nucleotide polymorphisms in MR and GR coding genes NR3C2 rs5522 and NR3C1 rs6198 respectively may be involved in smoking susceptibility The sample included 627 volunteers of which 514 were neversmokers and 113 lifetime smokers We report an interaction effect between rs5522 and rs6198 SNPs The odds ratio OR for the presence of the NR3C2 rs5522 Val allele in NR3C1 rs6198 G carriers was 018 P = 0007 while in rs6198 G noncarriers the OR was 183 P = 0027 We also found main effects of the NR3C1 rs6198 G allele on number of cigarettes smoked per day P = 0027 and in total score of the Fagerström Test for Nicotine Dependence P = 0007 These findings are consistent with a possible link between NR3C2 and NR3C1 polymorphisms and smoking behavior and provide a first partial replication for a nominally significant GWAS finding between NR3C2 and tobacco smokingThis work was supported by the following funding sources CNPq CAPES and FAPERGSDECITPPSUS We are thankful to Prof Paulo BelmontedeAbreu and Prof Luis A Rohde for providing administrative support in the Psychiatry Service of the Hospital de Clínicas de Porto Alegre
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