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MR and GR functional SNPs may modulate tobacco smoking susceptibility

  • Psychiatry and Preclinical Psychiatric Studies - Original Article
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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 never-smokers 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 0.18 (P = 0.007), while in rs6198 G noncarriers the OR was 1.83 (P = 0.027). We also found main effects of the NR3C1 rs6198 G allele on number of cigarettes smoked per day (P = 0.027) and in total score of the Fagerström Test for Nicotine Dependence (P = 0.007). 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 smoking.

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Acknowledgments

This work was supported by the following funding sources: CNPq, CAPES and FAPERGS-DECIT-PPSUS. We are thankful to Prof. Paulo Belmonte-de-Abreu and Prof. Luis A. Rohde for providing administrative support in the Psychiatry Service of the Hospital de Clínicas de Porto Alegre.

Conflict of interest

The authors have no biomedical financial interests or potential conflicts of interest to declare.

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Authors and Affiliations

  1. Department of Genetics, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Avenida Bento Gonçalves - 15053, Porto Alegre, RS, 91501-970, Brazil

    Diego L. Rovaris, Nina R. Mota, Lucas A. de Azeredo, Renata B. Cupertino, Guilherme P. Bertuzzi, Evelise R. Polina, Gustavo L. Kortmann, Sidia M. Callegari-Jacques & Claiton H. D. Bau

  2. ADHD Outpatient Program, Adult Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil

    Diego L. Rovaris, Nina R. Mota, Eduardo S. Vitola & Eugenio H. Grevet

  3. Postgraduate Program in Biotechnology, Centro Universitário UNIVATES, Lajeado, Brazil

    Verônica Contini

  4. Centre for Traumatic Stress Studies and Research (NEPTE), Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil

    Rodrigo Grassi-Oliveira

  5. Departament of Statistics, Instituto de Matemática, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

    Sidia M. Callegari-Jacques

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  1. Diego L. Rovaris
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  2. Nina R. Mota
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  4. Renata B. Cupertino
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  6. Evelise R. Polina
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  7. Verônica Contini
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Correspondence to Claiton H. D. Bau.

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Rovaris, D.L., Mota, N.R., de Azeredo, L.A. et al. MR and GR functional SNPs may modulate tobacco smoking susceptibility. J Neural Transm 120, 1499–1505 (2013). https://doi.org/10.1007/s00702-013-1012-2

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