Dietary Interactions and Risk of Non-Alcoholic Fatty Liver Disease: Epigenetics, Immune Factors and Gut Microbiome from Cohort Studies Across India

饮食相互作用和非酒精性脂肪肝的风险：来自印度队列研究的表观遗传学、免疫因素和肠道微生物组

• 批准号: MR/T008121/1
• 负责人: Gautam Mehta
• 金额: $ 6.42万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FT008121%2F1
• 关键词: Dietary; Interactions; Risk; Non; Alcoholic

Liver disease is one of the most important non-infectious diseases in the world today, causing 2 million deaths each year. It is particularly common in low and middle-income countries where it imposes a considerable burden on health-care systems. Some of this burden is due to chronic hepatitis B and C infection, although we now have the means to prevent and effectively treat these infections and many developed countries have set realistic targets for eradicating hepatitis C and preventing new cases of hepatitis B. As a result, the global burden of hepatitis-related liver disease is beginning to fall, but at the same time there have been marked increases in liver disease associated with obesity and excess alcohol consumption. Non-alcoholic fatty liver disease (NAFLD) is now the most common liver disease worldwide, and is also common throughout India although the number of people affected in a given area can vary from< 10% to > 50%. NAFLD is associated with obesity, and the majority of people with NAFLD develop fatty deposits in their liver. A small number of these go on to develop inflammation in their liver and this stage is called non-alcoholic steatohepatitis (NASH) and from there to cirrhosis the most serious form of liver injury.The majority of people with NAFLD are overweight and/or have the 'metabolic syndrome' which includes diabetes, raised blood cholesterol and high blood pressure. However, NAFLD can develop in people who do not have these features. We don't currently understand why some people with risk factors develop NAFLD and others do not. Additionally, Indian patients in particular can develop 'lean NAFLD', which occurs in the absence of obesity. This suggests that factors other than obesity and the metabolic syndrome may be important for the development of NAFLD and NASH in this population. These factors could include a person's genetic makeup, or the way in which their genes work- so-called epigenetic factors. In addition, the bacteria in the gut (the microbiome) are known to affect the way in which the body's immune system works and gut bacteria are often altered in patents with liver disease. None of these possible mechanistic factors have been studied in Indian populations. We have access to over 1000 people with NAFLD, and over 4000 people without NAFLD (acting as controls) from three sites in India. Extensive information is already available on their diet, alcohol intake, health history and blood test results as well as samples of their DNA. We plan to undertake 'Fibroscans' on the people recruited-a simple non-invasive test to determine how scarred the liver is, and also to look at their genes and alterations in epigenetics. This information, together with the information already available will be used to identify risk factors for NAFLD and NASH in this population. We will also undertake laboratory tests on urine, blood and stools from a smaller subset of people to explore alteration in the bacteria in the gut and the body's immune responses. This information may allow us to develop new treatments for this condition The information gathered during this project will provide us with a better understanding of the risk factors for developing NAFLD and NASH in India. It will allow identification of people at risk at an early stage so they can be advised to make appropriate life-style changes such as weight loss and diet modification. It will also provide information on the actual 'cause' of the condition which might allow development of drugs to treat those people in whom the condition is already established.

肝病是当今世界上最重要的非传染性疾病之一，每年造成200万人死亡。它在低收入和中等收入国家尤其普遍，给卫生保健系统造成相当大的负担。一些这方面的负担是由于慢性乙肝和丙肝感染,尽管我们现在有能力有效地预防和治疗这些感染和许多发达国家设定现实的目标,消除丙型肝炎和乙肝预防新发病例结果,hepatitis-related肝脏疾病的全球负担开始下降,但同时有显著增加肝脏疾病与肥胖和过量饮酒。非酒精性脂肪性肝病（NAFLD）现在是世界上最常见的肝脏疾病，在印度也很常见，尽管在特定地区受影响的人数从< 10%到50%不等。NAFLD与肥胖有关，大多数NAFLD患者的肝脏中存在脂肪沉积。其中一小部分继续发展为肝脏炎症，这一阶段被称为非酒精性脂肪性肝炎（NASH），并从那里发展为肝硬化，这是肝损伤最严重的形式。大多数NAFLD患者超重和/或患有“代谢综合征”，包括糖尿病、血胆固醇升高和高血压。然而，不具备这些特征的人也可能发生NAFLD。我们目前还不明白为什么一些有危险因素的人会发展为NAFLD，而另一些人不会。此外，印度患者尤其可能发展为“瘦型NAFLD”，这发生在没有肥胖的情况下。这表明除肥胖和代谢综合征外，其他因素可能对该人群中NAFLD和NASH的发展起重要作用。这些因素可能包括一个人的基因构成，或者他们的基因工作方式，即所谓的表观遗传因素。此外，肠道中的细菌（微生物组）已知会影响人体免疫系统的工作方式，并且肠道细菌经常在肝病患者中发生改变。这些可能的机械因素都没有在印度人群中进行过研究。我们从印度的三个地点访问了1000多名NAFLD患者和4000多名非NAFLD患者（作为对照）。关于他们的饮食、酒精摄入量、健康史、血液测试结果以及DNA样本，已经有了广泛的信息。我们计划对招募的人进行“纤维扫描”——一种简单的非侵入性测试，以确定肝脏的疤痕程度，并观察他们的基因和表观遗传学的变化。这些信息，连同已有的信息，将用于确定该人群中NAFLD和NASH的危险因素。我们还将对一小部分人的尿液、血液和粪便进行实验室测试，以探索肠道细菌和身体免疫反应的变化。该项目收集的信息将使我们更好地了解在印度发生NAFLD和NASH的危险因素。它可以在早期阶段识别出有风险的人，从而建议他们做出适当的生活方式改变，比如减肥和调整饮食。它还将提供有关这种疾病的实际“原因”的信息，这可能有助于开发药物来治疗那些已经患有这种疾病的人。

项目成果

A Genome-wide Association Study of non-alcoholic fatty liver disease in India: is there divergence in the genetic risk profile?

印度非酒精性脂肪肝的全基因组关联研究：遗传风险状况是否存在差异？

• 发表时间: 2020
• 作者: Doshi N