Asociación entre el polimorfismo rs9939609 del gen FTO con la ingesta energética, macronutrientes y consumo de alcohol en población chilena / Association of the FTO (rs9939609) genotype with energy intake

Background: Fat-mass-associated-gene (FTO) is associated with higher energy intake and specific food preferences. Aim: To investigate the association of the FTO genotype with energy intake, macronutrient and alcohol consumption. Material and Methods: Four hundred and nine participants of the GENADIO (Genes, Environment, Diabetes and Obesity) study were included. Energy intake, macronutrient and alcohol consumption were the outcomes of interest. The association of FTO (rs9939609) genotype with these outcomes was investigated using linear regression analyses, adjusting for confounding variables. Results: After adjusting for socio-demographic factors, being a carrier of the risk allele for the FTO gene was associated with a higher energy intake (173 kcal per each extra copy of the risk variant [95% confidence intervals (CI): 45; 301], (P = 0.008). After adjusting for lifestyle factors and body mass index, the association was slightly attenuated but remained significant (144 kcal [95% CI: 14; 274], p = 0.030). Conclusions: The FTO genotype is associated with a higher energy intake.

Farmacogenética, tabaco, alcohol y su efecto sobre el riesgo de desarrollar cáncer / Pharmacogenetics, tobacco, alcohol and its effect on the risk development cancer

El cáncer es la segunda causa de muerte en el mundo, según datos de la Organización Mundial de la Salud (OMS) en el año 2015 ocasionó 8,8 millones de muertes. Dentro de los factores de riesgo para el desarrollo de cáncer se encuentran el tabaquismo y el consumo de alcohol. En Chile el 33,6% de la población fuma y un 21,2 % de los jóvenes. El consumo de alcohol en la población chilena es de 74,5 % y en los jóvenes de un 12,2 %. Entre los factores fisiológicos que influyen en el desarrollo de cáncer, el factor genético juega un rol relevante, habiéndose demostrado que la presencia de polimorfismos genéticos alteran la capacidad del organismo de eliminar contaminantes y aumentan el riesgo de desarrollar cáncer. Lo mismo ocurre con polimorfismos que impiden la reparación de ADN debido a daños producidos por efecto de contaminantes ambientales como el humo de cigarrillo. El objetivo de esta revisión es analizar el estado del arte de la relación entre farmacogenética, tabaco y alcohol como factores de riesgo para el desarrollo de cáncer. Los resultados sugieren que la presencia de po limorfismos que alteran la función de enzimas de biotransformación fase I (CYP1A1, CYP1E1) y fase II (GST), además de polimorfismos en enzimas de reparación del ADN (ERCC1/ERCC2) aumentan el riesgo de cáncer inducido por el hábito tabáquico y alcohólico. Esta asociación es importante, si consideramos que en la población chilena el hábito de fumar y beber alcohol es altamente prevalente.

Cancer is the second leading cause of death in the world, causing 8.8 million deaths in 2015 according to the World Health Organization (WHO). Risk factors for cancer include smoking and alcohol con sumption. In Chile, 33.6% of the population and 21.2% of young people smokes. Alcohol consump tion in the Chilean population is 74.5% and 12.2% in young people. Among the physiological factors that influence the development of cancer, the genetic factor plays a relevant role. It has been shown that the presence of genetic polymorphisms that alter the ability of the body to eliminate contami nants increase the risk of developing cancer. The same applies to polymorphisms that prevent DNA repair due to damage caused by environmental pollutants such as cigarette smoke. The objective of this review is to analyze the state of the art of the relationship between pharmacogenetics, smoking, and alcohol consumption as risk factors for the development of cancer. In conclusion, the results suggest that the presence of polymorphisms that alter the function of biotransformation enzymes phase I (CYP1A1, CYP1E1) and phase II (GST), as well as polymorphisms in DNA repair enzymes (ERCC1 / ERCC2), increase the risk of cancer induced by smoking and alcohol consumption. This association is important considering that smoking and drinking alcohol are highly prevalent among the Chilean population.

Patrones de consumo y genotipos determinantes de la tolerancia al alcohol: estudio en estudiantes universitarios de Santiago de Chile / Alcohol consumption patterns and genotypes determining alcohol tolerance in Chilean university students

Background: Alleles involved in inefficient (ADH1B2*2 and ALDH2*2) or efficient (SNP6, ADH4 gene) alcohol metabolism may influence the risk of alcoholism. Alcoholism susceptibility has been classified as protector and risk-dependence phenotypes, associated with inefficient and efficient alcohol genetic metabolizing variants, respectively. Aim: To investigate the possible association between genetic protective and risk-dependence variants and alcohol intake patterns. Material and Methods: Saliva DNA samples were obtained and the AUDIT (Alcohol Use Disorders Identification Test) questionnaire was applied to 210 university students aged between 18 and 25 years old. Results: No statistically significant association between protective or risk-dependence genetic variants and alcohol pattern intake was detected. However, new categories of alcohol intake patterns-not included in the AUDIT questionnaire-were identified. Conclusions: No association between the protector and risk-dependence phenotypes and patterns of alcohol consumption was detected in this sample of students.

Alcohol dehydrogenase-2 and aldehyde dehydrogenase-2 genotypes, alcohol drinking and the risk of primary hepatocellular carcinoma in a Chinese population.

OBJECTIVE: To investigate the relationship of alcohol dehydrogenase-2 (ADH2) and aldehyde dehydrogenase-2 (ALDH2) genotypes as well as alcohol drinking to the susceptibility of primary hepatocellular carcinoma (HCC). METHODS: A case-control study including 208 cases of HCC and 208 controls matched with sex, age and residential area was carried out in Taixing city of Jiangsu province, China. Blood samples were collected and tested for ADH2 and ALDH2 genotypes by PCR-RFLP method. RESULTS: There were no significant differences in the frequency of either ADH2 or ALDH2 genotypes between cases and controls. Compared with no-drinkers possessing ALDH21*1 genotypes, drinkers with ALDH21*2 or ALDH22*2 genotypes and cumulative amount of alcohol consumption >3 (Kg * years) were at a significantly higher risk of developing HCC (OR=3.30, 95%CI: 1.24-8.83). In contrast, there was no significant difference in cancer risk between no-drinkers with ADH21*1 and drinkers with ADH2 1*2 or ADH22*2 genotypes. A dose-dependent positive result was found (P=0.044) between cumulative amount of alcohol consumption and the risk of HCC in individuals carrying ALDH21*2 or ALDH22*2 genotypes. Drinkers with cumulative amount of alcohol consumption >3 (Kg * years) who possessed both inactive ALDH2 (ALDH21*2 or ALDH22*2) and inactive ADH (ADH21*2 or ADH22*2) genotypes were not at a significantly higher risk of HCC (adjusted OR=4.26, 95%CI: 0.63-29.08) compared to no-drinkers possessing ADH21*1 and ALDH21*1 genotypes. Compared with individuals possessing ALDH21*1, with negative HBsAg and cumulative amount of alcohol consumption <or=3 (Kg * years), those with ALDH21*2 or ALDH22*2, positive HBsAg, and cumulative amount of alcohol consumption>3 (Kg * years) had a significantly higher risk of HCC (OR=49.71, 95%CI: 5.51-448.96). CONCLUSION: These results revealed that it was not ADH2 but ALDH2 polymorphisms that had a significant interaction with heavy alcohol consumption in the development of HCC. This result suggests that to help lower their risk for HCC , persons with ALDH21*2 or ALDH22*2 genotypes should be encouraged to reduce their consumption of alcoholic beverages.

Variantes alélicas de CYP1A1 y GSTM1 como biomarcadores de susceptibilidad a cáncer gástrico: influencia de los hábitos tabáquico y alcohólico / Cytochrome P4501A1 (CYP1A1), glutathione S transferase M1 (GSTM1) polymorphisms and their association with smoking and alcohol consumption as gastric cancer susceptibility biomarkers

Background: Gastric cancer (GaC) is the second cause of death by cancer in the world and one of the first causes in Chile. However, the burden of this disease shows remarkable worldwide variation probably explained by environmental and genetic factors. The role of susceptibility low penetrance genes and environmental and dietary factors in the etiology of gastric cancer is not well-known. Aim: To analyze the possible association between CaG susceptibility, genetic (CYP1A1 and GSTM1 polymorphisms) and environmental (tobacco and alcohol) factors. Patients and Methods: In a case-control study, we included 73 patients with a pathologically diagnosed GaC and 263 controls. DNA was extracted from peripheral blood to detect allele variants for CYP1A1 and GSTM1, using polymerase chain reactions and digestion with restriction enzymes. Results: There was a clear association of smoking and alcohol ingestion with GaC with odds ratios (OR) of 2.54 (95 percent confidence intervals (CI) of 1.45-4.46 and OR of 3.36 (95 percent CI 1.76-6.41), respectively. Polymorphic variants of CYP1A1 and GSTM1 had no association with GaC. However, the m2 variant of CYP1A1 significantly modifies the risk induced by tobacco or alcohol (OR 13.65; 95 percent CI 3.15-59.05 y 8.37; 95 percent CI 1.86-37.64, respectively). Conclusions: Subjects that carry the m2 allelic variant of CYP1A1 and are exposed to tobacco smoke or alcohol have a significantly higher risk of developing gastric cancer.

O papel da genética na dependência do álcool / The role of genetics in alcohol dependence

Este artigo procura examinar a questão da herdabilidade na dependência do álcool. Através da revisão de estudos em famílias, em gêmeos e de adocão, encontramos evidências para afirmar a importância dos fatores genéticos na transmissão da vulnerabilidade a esta dependência. Essa transmissão pode ser melhor compreendida através de um modelo epigenético de desenvolvimento do transtorno, no qual condicões biológicas hereditárias associem-se a situacões ambientais ao longo da vida para a producão da dependência. Neste artigo, apresentamos essas condicões biológicas intermediárias vinculadas ao alto risco para dependência do álcool. Por fim, descrevemos os estudos moleculares que vêm estabelecendo associacões entre polimorfismos e a dependência do álcool, com relevo para o sistema dopaminérgico.

Antecedentes familiares na determinaçäo da gravidade do alcoolismo / Familial antecedents as a determinant of severity of alcoholism

Alguns estudos têm demonstrado diferenças significantes entre alcoólicos com um histórico familiar positivo para alcoolismo (HFP) e aqueles com histórico familiar negativo para alcoolismo (HFN), e que um passado de história familiar de alcoolismo pode influenciar o curso e a gravidade da doença. Tendo em vista a escassez deste tipo de investigaçäo neste País, decidimos levar a cabo uma pesquisa, coletando dados de uma amostra de 110 alcoolistas de 6 diferentes instituiçöes do Rio de Janeiro, de ambos os sexos, faixa etária e nível sócio-econômico diversos. Usando um questionário como instrumento, reunimos informaçöes sobre o histórico familiar para alcoolismo, hábitos de bebida e consumo de álcool, assim como dados sobre a idade do início do beber e do aparecimento dos primeiros problemas com a bebida, sexo, educaçäo e ocupaçäo dos testandos. Em nosso estudo encontramos 68 indivíduos com histórico familiar positivo para alcoolismo e 42 sem tal antecedente. Análises estatísticas dos dois grupos mostraram que o grupo HFP apresentou formas mais graves de dependência. As variáveis demográfica e social, a idade do início do beber e a idade dos primeiros problemas com a bebida näo diferiram significativamente entre os dois grupos. Pesquisas futuras com outros grupos de risco para alcoolismo podem ajudar a lançar luz sobre os vários e complexos aspectos da dependência do álcool