Genetic and Environmental Risk of Liver Disease/Cancer among Mexicans

墨西哥人肝病/癌症的遗传和环境风险

• 批准号: 9753952
• 负责人: Yvonne Nicole Flores
• 金额: $ 16.09万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-15 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9753952
• 关键词: Adult; African American; Alcoholic Liver Diseases; Alleles; Apolipoproteins B; Bariatrics; CETP gene; CSPG3 gene; CYP2E1 gene; Candidate Disease Gene; Carcinoma; Cirrhosis; Cities; Clinic; Clinical; Cohort Studies; Complex; Data; Development; Diabetes Mellitus; Disease Progression; Environmental Risk Factor; Ethnic Origin; Fatty Liver; Frequencies; Future; Genes; Genetic; Genetic Predisposition to Disease; Genetic Risk; Genetic study; Goals; Grant; Health; Hepatitis B; Hepatitis C; Hispanics; IL6 gene; Incidence; Indigenous; Infection; Inflammation; Insulin Resistance; Insulin Resistance Pathway; Knowledge; Latino; Liver diseases; Malignant Neoplasms; Malignant neoplasm of liver; Medical Genetics; Mentors; Metabolic syndrome; Mexican; Mexican Americans; Mexico; Modification; Molecular Epidemiology; Nested Case-Control Study; Not Hispanic or Latino; Obesity; Oxidative Stress; PPARG gene; Population; Populations at Risk; Predisposition; Prevalence; Questionnaires; Race; Research; Research Personnel; Research Project Grants; Research Proposals; Risk; Risk Factors; Role; SLC2A1 gene; STAT3 gene; STAT4 gene; Sampling; Single Nucleotide Polymorphism; Steatohepatitis; TNF gene; Therapeutic Intervention; Time; Training; cancer health disparity; career development; caucasian American; design; gene interaction; genetic epidemiology; genetic risk factor; high risk; improved; lipid metabolism; liver development; non-alcoholic fatty liver disease; nonalcoholic steatohepatitis; prevent; prophylactic; public health relevance; skills

 DESCRIPTION (provided by applicant): This career development and research proposal is designed to provide me with specialized training and mentored guidance that will help me become an independent cancer investigator. The overall aim of my research project is to investigate the role of genetic influence on the development of liver disease/cancer in a sample of Mexican adults, an understudied, at-risk population. This research project will provide an ideal opportunity to apply the specialized knowledge and skills in genetic and molecular epidemiology that I will obtain as part of my proposed career development activities. Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are earlier forms of liver disease that can progress to liver cancer. The prevalence of NAFLD, NASH and liver cancer is highest among Latinos, followed by Caucasians and African Americans. Known risk factors for NAFLD and NASH include obesity, metabolic syndrome, diabetes mellitus, and insulin resistance. Although the environmental risk factors for NAFLD and NASH are well established, the genetic basis of hepatic steatosis is largely unknown. Even less is known about the genetic factors that contribute to liver disease/cancer susceptibility among Latinos, despite the disproportionate burden of liver cancer among this group. The main goal of this research project is to explore how genetic susceptibility may interact with known risk factors (e.g. obesity metabolic syndrome, and diabetes) to increase risk of NAFLD and NASH among Mexican adults. A nested case-control study will be conducted using a sample of 480 cases (180 NAFLD and 300 NASH, all clinically confirmed) and 480 healthy controls from central Mexico. The existing clinical, genetic, and questionnaire data obtained in 2011-2013 as part of the Mexican Health Worker Cohort Study (MHWCS) and from a bariatric clinic in Mexico City will be integrated. The main hypothesis of this research is that the effect of obesity, metabolic syndrome, and diabetes on increased risk of NAFLD and NASH will be greater in the presence of high-risk single-nucleotide polymorphism (SNPs) such as PNPLA3 (rs738409). A better understanding of the mechanisms underlying the genetic and environmental factors that are associated with an increased risk of NAFLD and NASH may help to reduce liver cancer disparities among Latinos. The results of this study could also provide new targets for prophylactic and therapeutic interventions. Since Mexican-Americans are at increased risk of liver disease/cancer it is particularly important to investigate the mechanisms through which genes influence disease progression in this population. By finding better ways to identify and treat NAFLD and NASH at the earlier stages of liver disease we can help prevent future cases of liver cancer.

 描述（由适用提供）：这项职业发展和研究建议旨在为我提供专门的培训和修改指导，这将帮助我成为独立的癌症研究者。我的研究项目的总体目的是研究遗传影响对墨西哥成年人样本的肝脏疾病/癌症发展的作用，这是一种理解，处于危险中。该研究项目将提供理想的机会，以应用遗传和分子流行病学的专业知识和技能，作为我提议的职业发展活动的一部分。非酒精性脂肪肝病（NAFLD）和非酒精性脂肪性肝炎（NASH）是早期可以发展为肝癌的肝病的形式。 NAFLD，NASH和肝癌的患病率在拉丁美洲裔中最高，其次是高加索人和非裔美国人。 NAFLD和NASH的已知危险因素包括肥胖，代谢综合征，糖尿病和胰岛素抵抗。尽管NAFLD和NASH的环境危险因素已经建立了良好，但肝脂肪变性的遗传基础在很大程度上是未知的。关于有助于拉丁美洲裔肝病/癌症易感性的遗传因素的知之甚少，这一组中肝癌的燃烧不成比例。该研究项目的主要目标是探索遗传易感性如何与已知危险因素（例如肥胖代谢综合征和糖尿病）相互作用，以增加墨西哥成年人中NAFLD和NASH的风险。将使用480例病例（180例NAFLD和300 NASH，all Cluin ny Cluin Sunders Sunders nash）和480个来自墨西哥中部的健康对照的样本进行嵌套的病例对照研究。作为墨西哥卫生工作者队列研究（MHWCS）以及墨西哥城的一家减肥诊所的一部分，2011 - 2013年获得的现有临床，遗传和问卷数据将集成。这项研究的主要假设是，在存在高风险的单核苷酸多态性（SNP）（例如PNPLA3）（例如PNPLA3）（rs738409）的情况下，肥胖，代谢综合征和糖尿病对增加NAFLD和NASH风险的影响将更大。更好地了解与NAFLD和NASH风险增加有关的遗传和环境因素的机制可能有助于减少拉丁美洲裔之间的肝癌分布。这项研究的结果还可以为预防性和治疗性干预提供新的目标。由于墨西哥裔美国人的肝病/癌症风险增加，因此研究基因影响该人群疾病进展的机制尤为重要。通过找到更好的方法来识别和治疗NAFLD和NASH在肝病的早期阶段，我们可以帮助预防将来的肝癌病例。

项目成果

Genetic variants in COL13A1, ADIPOQ and SAMM50, in addition to the PNPLA3 gene, confer susceptibility to elevated transaminase levels in an admixed Mexican population.

• DOI: 10.1016/j.yexmp.2018.01.001
• 发表时间: 2018-03
• 期刊: Experimental and molecular pathology
• 影响因子: 3.6
• 作者: Larrieta-Carrasco E;Flores YN;Macías-Kauffer LR;Ramírez-Palacios P;Quiterio M;Ramírez-Salazar EG;León-Mimila P;Rivera-Paredez B;Cabrera-Álvarez G;Canizales-Quinteros S;Zhang ZF;López-Pérez TV;Salmerón J;Velázquez-Cruz R
• 通讯作者: Velázquez-Cruz R

Influence of mealtime habits on the risk of weight gain and obesity in Mexican adults.

• DOI: 10.1017/s1368980016002184
• 发表时间: 2017-03
• 期刊: Public health nutrition
• 影响因子: 3.2
• 作者: Dosamantes-Carrasco LD;Méndez-Hernández P;Flores YN;Siani C;Denova-Gutiérrez E;Gallegos-Carrillo K;Ramírez P;Rivera-Paredez B;Salazar-Martínez E;Salmerón J
• 通讯作者: Salmerón J

Association between Vitamin D Deficiency and Single Nucleotide Polymorphisms in the Vitamin D Receptor and GC Genes and Analysis of Their Distribution in Mexican Postmenopausal Women.

• DOI: 10.3390/nu10091175
• 发表时间: 2018-08-27
• 期刊: Nutrients
• 影响因子: 5.9
• 作者: Rivera-Paredez B;Macías N;Martínez-Aguilar MM;Hidalgo-Bravo A;Flores M;Quezada-Sánchez AD;Denova-Gutiérrez E;Cid M;Martínez-Hernández A;Orozco L;Quiterio M;Flores YN;Salmerón J;Velázquez-Cruz R
• 通讯作者: Velázquez-Cruz R

Association of GC Variants with Bone Mineral Density and Serum VDBP Concentrations in Mexican Population.

• DOI: 10.3390/genes12081176
• 发表时间: 2021-07-29
• 期刊: Genes
• 影响因子: 3.5
• 作者: Rivera-Paredez B;Hidalgo-Bravo A;León-Reyes G;Antuna-Puente B;Flores YN;Salmerón J;Velázquez-Cruz R
• 通讯作者: Velázquez-Cruz R

Total, Bioavailable, and Free 25-Hydroxyvitamin D Equally Associate with Adiposity Markers and Metabolic Traits in Mexican Adults.

• DOI: 10.3390/nu13103320
• 发表时间: 2021-09-23
• 期刊: Nutrients
• 影响因子: 5.9
• 作者: Rivera-Paredez B;Hidalgo-Bravo A;León-Reyes G;León-Maldonado LS;Aquino-Gálvez A;Castillejos-López M;Denova-Gutiérrez E;Flores YN;Salmerón J;Velázquez-Cruz R
• 通讯作者: Velázquez-Cruz R