Role of genetic susceptibility in nicotine addiction and chronic obstructive pulmonary disease

Abstract Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality in developed countries. Although cigarette smoking is the major risk factor, only 10-20% of smokers develop COPD. The extent of cigarette smoking (pack-years and smoking duration) accounts for only 15% of the variation in lung function, indicating that differences in susceptibility to COPD must exist. We provide an overview of the complexity of nicotine addiction and COPD, with special attention to the involvement of genetic factors. The following aspects are discussed in the present article: (1) epidemiology in Mexico and (2) a review of the published literature on genetic association studies using the National Center for Biotechnology Information database of the United States as a search tool. COPD is unique among complex genetic diseases where an environmental risk factor is known and the level of exposure can be documented with some precision. The high morbidity and mortality associated with COPD and its chronic and progressive nature has prompted the use of molecular genetic studies to identify susceptibility factors for the disease. Biomedical research has a remarkable set of tools to aid in the discovery of genes and polymorphisms. We present a review of the most relevant genetic associations in nicotine addiction and COPD.

Effect of MDR C3435T polymorphism on Varenicline treatment in quit smoking

Despite so many global efforts, smoking still remains to be one of the most common addictions worldwide. Even though most smokers wish to quit smoking, many of them fail. In this respect, genetic variants are thought to be remarkable factors in nicotine dependence and in treatment of smoking cessation. This is a paper investigating a single variant p-glycoprotein (P-gp) polymorphisms and its effect on Varenicline efficacy in the smoking cessation. 158 smokers and 52 non-smoker healthy volunteers were included. We determined the P-gp C3435T gene polymorphisms in all subjects. Face to face interviews with smokers were performed for smoking cessation and Varenicline was given for smoking cessation. Cessation success was evaluated in the 6th month and success rates were compared according to the P-gp genotype distributions. In our study, smoking cessation rate by Varenicline was 57.0%. This rate was 55.0% in females, and 57.2% in males (p=0.85). The P-gp C3435T gene distribution was similar in control, quitters and not-quitter groups. Cessation rate was at highest point in genotype CT (62.2%) and at the lowest in TT (47.6%). It was 53.8% in genotype CC and there was no statistically significant difference (p=0.27). Our results suggest that genetic variants of P-gp C3435T did not significantly affect Varenicline treatment for smoking cessation.

Variantes genéticas de CYP2A6 y su relación con la dependencia tabáquica y el hábito de fumar en una muestra individuos chilenos: Un estudio piloto / Relation of genetic variants of CYP2A6 with tobacco dependence and smoking habit in Chilean subjects: A pilot study

Background: Genetic and metabolic factors associated with nicotine metabolism may be related to smoking behavior. Aim: To assess the prevalence of allelic and genotype variants of CYP2A6 in a sample of Chilean subjects and to evaluate their relationship with smoking and tobacco dependence. Material and Methods: The genotype frequencies for *2, *3 and *4 of CYP2A6*1 (wild type) gene were determined by polymerase chain reaction (PCR) in 54 volunteers. Addiction to tobacco was evaluated using the Fagerstrom Test. The association between the presence of allelic variants of CYP2A6 and smoking and tobacco dependence was evaluated with chi square test. Results: The prevalence of *1, *2 (wt/*2), *3 (wt/*3 or *31*3) and *4 (del/del) were 92.6%, 3.7%, 0% y 3.7%, respectively. No significant association was observed between being a carrier of a variant genotype of CYP2A6 and smoking or tobacco dependence. Conclusions: In this sample of Chilean individuals we did not find a relation between any CYP2A6 genotype with smoking or tobacco dependence.

Caracterización clínica de pacientes intervenidos con Stent medicado y Stent convencional / Clinical features of patients with drug-eluting stent and bare-metal stent

Objetivo: Caracterizar clínicamente a los pacientes intervenidos con stent medicado y convencional en el año 2004, en la Unidad Cardiovascular de la Clínica Medellín. Métodos: Estudio Cross-sectional, realizado con base en las historias clínicas de 157 pacientes, intervenidos con stent en la Clínica Medellín en el año 2004 a los cuales se les hizo la caracterización de acuerdo al stent implantado. Resultados: De los 157 pacientes, 61,1% fueron hombres; a 23.3% de los pacientes se les implantó stent medicado y a 77,7% stent convencional. Como antecedentes patológicos se encontró hipertensión arterial en el 63,7%, diabetes mellitus en el 24,2%, Y dislipidemia en 38,2%. Los síntomas postquirúrgicos mas frecuentes fueron angina 11.5% y dolor precordiall 0,2%. La muerte ocurrió en 9 pacientes (5,7%), de los cuales ocho (88,9%) tenía stent convencional y 11,1% medicado. Los stents convencionales se implantan con mayor frecuencia en pacientes adultos mayores, de sexo masculino con antecedentes personales de tabaquismo e hipertensión arterial y con antecedentes familiares de enfermedad coronaria. En pacientes con infarto agudo del miocardio se prefiere usar stent convencional. La complicación más importante es el síndrome coronario y un número muy limitado de pacientes muere por causas relacionadas con el stent.

Objective: To characterize the clinical features of patients intervened with either medicated or conventional stent in 2004, at the Cardiovascular Unit of Clinica Medellín. Methodology: Cross sectional descriptive study of 157 patients intervened with stent in the Clinica Medellin during 2004. Patients were analyzed according to the implanted stent. Results: From the 157 patients, 96 were men (61.1%). The implanted stent was medicated in 23.3% and conventional in 77,7%. In terms of comorbidities hypertension was found in 63,7%, diabetes in 24,2 and dyslipidemia in 38,2%. The most frequen postsurgical symptoms were angina in 11.5% and chest pain in 10,2%; 5.7% patients died, 88.9% of them with conventional stent, 11.1 % drug-eluting stent, and one case related to the implantation by itself.

A influência da genética na dependência tabágica e o papel da farmacogenética no tratamento do tabagismo / The influence of genetics on nicotine dependence and the role of pharmacogenetics in treating the smoking habit

Mesmo com os esforços intensivos para o controle do tabagismo nas últimas décadas, uma proporção substancial de pessoas inicia a fumar ou mantém-se fumando apesar do pleno conhecimento dos malefícios do hábito. Os estudos têm focado atualmente as bases genéticas da adição nicotínica. O tabagismo tem sido associado a vários polimorfismos genéticos, mas os fatores ambientais também devem ser enfatizados. Esta revisão apresenta alguns dos principais dados disponíveis dos estudos genéticos sobre o comportamento tabágico. Esta linha de pesquisa poderá, no futuro, ajudar os clínicos a individualizar o tipo, a dosagem e a duração do tratamento da dependência tabágica, conforme o genótipo de cada fumante, maximizando a eficácia do esquema proposto.

Despite the considerable efforts made in the fight against smoking in the last decades, there are still substantial numbers of people who, in full knowledge of the health hazards, begin smoking or continue smoking. Recent studies have focused on the genetic bases of the nicotine addiction. Various genetic polymorphisms have been associated with smoking. However, environmental factors have also been shown to play a role. In this review, we present some of the principal data collected in genetic studies of smoking behavior. The results obtained through this line of research will eventually aid clinicians in individualizing the type, dosage and duration of treatment for patients with nicotine dependence in accordance with the genotype of each smoker, thereby maximizing the efficacy of the proposed treatment regimen.

Evaluación de hipermetilación del gen p16INK4alfa en cáncer escamoso de pulmón en pacientes chilenos / Hypermethylation of gene p16INK4alpha in chilean patients with squamous cell lung carcinoma

The silencing of p16INK4a (p16) tumor suppressor gene by aberrant methylation has been described as a common event in human tumoral types, such as squamous cell lung carcinoma (SCLC). This is a very frequent histological type in Chile, usually associated to chronic smokers. The purpose of this study was to investigate the p16 methylation status in patients with SCLC. Using a MSP (methylation-specific PCR), we determined that 25 out of 29 (86 percent) of SCLC patients had hypermethylation of p16 gene. There was also a significant concordance between hypermethylation of p16 gene and the presence of SCLC (p = 0.00005). According to our results, smokers have a 202-fold higher risk to develop SCLC than no-smokers (odds ratio, 201,7; 95 percent confidence interval, 7.18-5593). Therefore, our results suggest that hypermethylation of p16 gene is an useful prognostic marker in chronic smokers candidates to develop SCLC and patient with clinic suspicion of SCLC.

El silenciamiento génico por metilación aberrante del gen p16INK4a (p16) ha sido descrito en varios tipos de tumores humanos, como por ejemplo, el carcinoma escamoso de pulmón (CEP), un tipo histológico frecuente en Chile, asociado a tabaquismo crónico. El propósito de este estudio fue determinar el estado de metilación de la región promotora de p16 en CEP. Utilizando un método de PCR específico para metilación, se determinó que un total de 29 pacientes con CEP, 25 (86 por ciento) tenían el gen p16 hipermetilado. Además, se encontró una correlación significativa entre la hipermetilación del gen p16 y la presencia de CEP (p = 0,00005). Por otra parte, estimamos que los individuos fumadores tienen 201,7 veces más riesgo que los no fumadores de desarrollar CEP (odds ratio, 201,7; intervalo de confianza 95 por ciento, 7,18-5.593). Nuestros resultados sugieren que la detección de hipermetilación del gen p16 podría ser utilizada como un marcador molecular de diagnóstico precoz en individuos fumadores con riesgo a desarrollar CEP y en pacientes con sospecha clínica de CEP.

A historia familial e a prevalencia de dependencia de alcool e tabaco em area metropolitana na regiao Sul do Brasil / Familial history and prevalence of alcohol and tobacco dependence in a metropolitan area of southern Brasil

No presente estudo, foram analisadas a historia familial e a prevalencia de dependencia de alcool e tabaco nas regioes Norte, Sul e Oeste da cidade de Londrina, estado do Parana, Sul do Brasil, com uma populacao estimada de 277.391 habitantes, por meio de uma amostra aleatoria de 4.280 residencias, totalizando 42.517 pessoas...