Fatty Liver Disease in African Americans

肥胖是一个主要的健康问题，在美国和世界范围内，肥胖症的流行率正在上升， 对非裔美国人的影响不成比例。它可导致非酒精性脂肪性肝病(NAFLD)，在 转化可通过慢性肝炎导致肝癌，但恶性肿瘤直到晚期才会出现症状。 没有治愈的选择，导致极高的死亡率。另一方面，不断增长的知识 非酒精性脂肪肝致癌机制的研究为早期血清的研究提供了可能 可以将患者分为高风险患者和低风险患者的标志物：反过来，高风险患者可以经历 对肝癌进行监测，以便及早发现，以便进行根治性手术。本提案是一项合作性提案 霍华德大学(HU)和隆巴迪综合癌症中心(LCCC)的研究方法 乔治城大学发现受干扰的代谢和基因特征 接受医疗护理的非裔美国人(AA)人群中NAFLD患者的机械途径 霍华德大学医院的这种情况。我们的总体目标是确定候选基因和 与NAFLD相关的遗传途径，以发现和填补这种极端健康的知识空白 华盛顿特区各地戒酒协会之间的差距问题。这项初步研究的两个PI--Dr。 LCCC癌症流行病学家Christopher Loffredo和胃肠病专家兼主席Charles Howell博士 霍华德大学内科博士-将与HU的早期研究员Ghosh博士共同指导。Dr。 戈什的专长是慢性病的分子遗传学。利用这些互补的领域 专业知识，我们建议使用P20提案的试点资金招募50名非酒精性脂肪肝患者(病例)和50名 霍华德大学的配对对照：他们将参加面试，提供个人信息 和病史，并同意抽血以评估基因水平的差异 在与癌症相关的机制途径(如炎症)中的表达是潜在的 疾病进展为肝癌。我们将积极让研究生和博士后参与到 实验室工作。在特定目标1中，我们将应用基因表达分析(微阵列与IPA耦合 分析)揭示两组受试者的差异基因表达及其途径。在……里面 具体目标2我们将通过应用高通量TaqMan®Low来验证候选疾病标记物 密度阵列(TLDA)。我们将验证特定生物途径中的精确基因组合 我们将整合临床、流行病学和实验室数据，以确定这些标志物的稳健性 对这种新的TLDA方法的稳定性、有效性、重复性、可行性和实用性进行了研究。越界的人 因此，这项研究的目标是阐明NAFLD可能通过哪些机制做出贡献 重要的癌前通路的失调。反过来，这些知识将促进对 为这一少数群体提供治疗和预防的潜在途径。

Obesity is a major health concern that is increasing in prevalence in the U.S. and worldwide, and disproportionately affects African Americans. It can lead to non-alcoholic fatty liver disease (NAFLD), which in turn can lead to liver cancer via chronic hepatitis, but the malignancy is asymptomatic until late stage when curative options are unavailable, leading to extremely high mortality. On the other hand, increasing knowledge of the mechanistic pathways by which NAFLD leads to cancer offers the possibility to develop early serum markers that can stratify patients into those at higher and lower risk: in turn, higher risk patients can undergo liver cancer surveillance to identify it early enough for curative surgery. The present proposal is a collaborative approach for research at Howard University (HU) and the Lombardi Comprehensive Cancer Center (LCCC) at Georgetown University to discover the molecular and genetic signatures of perturbed metabolic and mechanistic pathways in NAFLD patients in an African–American (AA) population receiving medical care for this condition at Howard University Hospital. Our overall objective is to identify candidate genes and genetic pathways associated with NAFLD, to find and fill the knowledge gaps of this extreme health disparity issue among AA around the Washington DC region. The two PIs of this pilot study – Dr. Christopher Loffredo, a cancer epidemiologist at LCCC, and Dr. Charles Howell, a gastroenterologist and Chair of Internal Medicine at Howard University – will co-mentor Dr. Ghosh, an early stage investigator at HU. Dr. Ghosh's expertise is molecular genetics of chronic diseases. Leveraging these complementary areas of expertise, we propose to use pilot funding from this P20 proposal to enroll 50 NAFLD patients (cases) and 50 matched controls at Howard University: they will participate in an interview to provide information on personal and medical history, and will agree to a blood draw that will allow us to assess differences in levels of gene expression in cancer-relevant mechanistic pathways (e.g. inflammation) that are potential signatures of disease progression towards liver cancer. We will actively involve graduate and post-doctoral students in the laboratory work. In Specific Aim 1 we will apply a gene expression analysis (microarray coupled with IPA analysis) to divulge the differential gene expressions and their pathways in the two groups of subjects. In Specific Aim 2 we will validate the candidate disease markers by applying high-throughput TaqMan® Low Density Arrays (TLDA). We will validate the precise panel of genes within the particular biological pathways and we will integrate clinical, epidemiologic and laboratory data to identify the robustness of these markers towards stability, validity, reproducibility, feasibility and utility of this new TLDA approach. The overreaching goal of this research is, therefore, to shed new light on possible mechanisms by which NAFLD may contribute to the dysregulation of important pre-cancer pathways. In turn, such knowledge will foster the identification of potential avenues for treatment and prevention for this minority population.