Molecular and Genetic Signatures of Perturbed Diabetic Pathways with Hepatitis C Virus infection and Co-morbidity Risks in African American Population

项目1摘要 丙型肝炎病毒(丙型肝炎病毒)感染和2型糖尿病是两个主要的健康问题， 对服务不足的社区造成严重的健康差距，特别是非洲裔美国人(AA)，他们作为 A组，患有这两种疾病的比例在美国最高。我们的总体目标是确定候选人 2型糖尿病和丙型肝炎合并的相关基因和遗传途径。其背后的基本原理是 这项研究得到了大量证据的支持，这些证据支持这样的假设，即丙型肝炎病毒感染会使病情恶化 糖尿病患者的代谢和胰岛素抵抗异常，导致更不利的健康 结果。我们建议通过识别受干扰的基因和遗传途径来检验这一假说 与无丙型肝炎的T2 DM患者相比，这两种疾病并存。我们独特的资源环境 协作为研究这些问题提供了无与伦比的机会。具体目标1是招收 居住在华盛顿特区的AA人群中T2 DM患者的临床人群：一组 有丙型肝炎病毒的一组和没有丙型肝炎病毒的一组。我们将应用基因表达分析(微阵列与IPA耦合 分析)揭示这两组之间的差异基因表达及其途径。全球基因 将通过微阵列分析评估循环白细胞中的表达。具体目标2是 通过应用高通量TaqMan®低密度阵列(TLDA)验证候选疾病标记物。我们 将验证特定生物途径中的精确基因小组，我们将整合临床， 流行病学和实验室数据，以确定这些标志物对稳定性、有效性、 这种新的TLDA方法的重复性、可行性和实用性。这项研究的超常目标是， 因此，为了阐明丙型肝炎病毒可能导致疾病负担的可能机制， 为这一少数群体寻找治疗和预防2型糖尿病患者的方法。这个 这项研究的超乎寻常的目标是阐明丙型肝炎病毒可能参与的可能机制 T2 DM的疾病负担，而不仅仅是糖尿病造成的负担，并确定潜在的途径 在非裔美国人人口中的治疗和预防，从而为执行 HU RCMI解决少数民族健康差距问题。

Project 1 Summary Hepatitis C Virus (HCV) infection and type 2 diabetes mellitus (T2DM) are two major health concerns that are causing profound health disparities for underserved communities, particularly African-Americans (AA) who, as a group, suffer the highest rates of both diseases in the U.S. Our overall objective is to identify candidate genes and genetic pathways associated with the combination of T2DM and HCV. The rationale behind the study is informed by an emerging body of evidence supporting the hypothesis that HCV infection worsens the metabolic and insulin resistance abnormalities of diabetic patients, leading to even more unfavorable health outcomes. We propose to test this hypothesis by identifying the genes and genetic pathways perturbed by coexistence of the two diseases, in comparison to T2DM patients free of HCV. Our unique resource setting and collaboration provides an unmatched opportunity for examining these questions. Specific Aim 1 is to enroll a clinical population of subjects with T2DM in AA persons residing in the Washington, DC region: one group with HCV and one group without it. We will apply a gene expression analysis (microarray coupled with IPA analysis) to divulge the differential gene expressions and their pathways in those two groups. Global gene expression will be assessed in circulating white blood cells through microarray assays. Specific Aim 2 is to validate the candidate disease markers by applying highthroughput 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 HCV may contribute to the disease burden of patients with T2DM, and identify avenues for treatment and prevention, for this minority population. The overreaching goal of this research is to shed new light on possible mechanisms by which HCV may contribute to the disease burden of T2DM, beyond that attributable to diabetes alone, and identify potential avenues for treatment and prevention in the African-American population, thereby contributing positively to the mission of HU RCMI to address minority health disparities.