Glutamate and Synaptic Plasticity Systems and Smoking Behavior: Results from a Genetic Association Study

Smoking behavior is a multifactorial phenotype with significant heritability. Identifying the specific loci that influence smoking behavior could provide important etiological insights and facilitate the development of treatments to further reduce smoking related mortality. Although several studies pointed to different candidate genes for smoking, there is still a need for replication especially in samples from different countries. In the present study, we investigated whether 21 positive signals for smoking behavior from these studies are replicated in a sample of 531 blood donors from the Brazilian population. The polymorphisms were chosen based on their representativeness of different candidate biologic systems, strength of previous evidence, location and allele frequencies. By genotyping with the Sequenom MassARRAY iPLEX platform and subsequent statistical analysis using Plink software, we show that two of the SNPs studied, in the SLC1A2 (rs1083658) and ACTN1 (rs2268983) genes, were associated with smoking behavior in our study population. These genes are involved in crucial aspects of nicotine dependence, glutamate system and synaptic plasticity, and as such, are biologically plausible candidates that merit further molecular analyses so as to clarify their potential role in smoking behavior

Associa??o do polimorfismo Gln223Arg do receptor da leptina com ?ndice de massa corporal e status tab?gico

Made available in DSpace on 2015-04-14T13:34:26Z (GMT). No. of bitstreams: 1 398705.pdf: 778724 bytes, checksum: c4b0e318c79d4fef0ca689429b5a3f5c (MD5) Previous issue date: 2007-12-19INTRODU??O: Estudos comprovando os malef?cios do fumo t?m sido amplamente difundidos como forma de combate ? adi??o. Mas existe grande dificuldade para sua cessa??o. Um dos fatores ? o ganho de peso decorrente deste ato. Estudos de polimorfismos no gene do receptor da leptina sugerem a associa??o dos mesmos ? composi??o corporal e ? distribui??o da gordura no corpo; mas tal mecanismo ainda n?o est? bem definido quando a vari?vel status tab?gico ? inclu?da. OBJETIVO: Verificar a associa??o entre status tab?gico, IMC e o polimorfismo LEPR Gln223Arg. M?TODOS: Foram selecionados 742 volunt?rios no banco de sangue da cidade de Passo Fundo, RS. Os participantes respondiam a um question?rio e coletava-se uma amostra de sangue. Ap?s foi feita a extra??o do DNA, seguido da t?cnica de rea??o em cadeia da polimerase, e, para a genotipagem , a t?cnica de polimorfismos de tamanhos de fragmentos de restri??o com endonuclease de restri??o. Para as an?lises, utilizou-se o teste qui-quadrado de Pearson, com signific?ncia de 5%. RESULTADOS: Foi constatada associa??o positiva entre o polimorfismo Gln223Arg do LEPR, IMC e status tab?gico em obesos com o gen?tipo Arg/Arg. N?o foi verificada associa??o entre o polimorfismo Gln223Arg do LEPR e IMC. N?o houve associa??o entre o polimorfismo Gln223Arg do LEPR e status tab?gico. CONCLUS?O: Estes achados sugerem que nos indiv?duos com IMC maior ou igual a 30 kg/m2, o tabagismo se distribui de forma diferente conforme o polimorfismo Gln223Arg do LEPR, sendo os obesos com o gen?tipo Arg/Arg os que tiveram maior propor??o de fumantes (P = .03)

Genetic association data for 21 candidate SNPs for smoking behavior.

<p>F_A: risk allele frequency in affected cases.</p><p>F_U: risk allele frequency in unaffected controls.</p

Demographic characteristics of study subjects.

*<p>P = 0.02.</p>**<p>P = 0.002.</p>***<p>FTND = Fagerstrom Test for Nicotine Dependence: Moderate/High (4–10) vs Low dependence nicotine level scores (0–3).</p