Clinical, Molecular, and Genetic Determinants of MRI-determined Left Atrial Phenotypes

MRI 确定的左心房表型的临床、分子和遗传决定因素

• 批准号: 10412884
• 负责人: JORGE R KIZER
• 金额: $ 1.97万
• 依托单位: NORTHERN CALIFORNIA INSTITUTE/RES/EDU
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10412884
• 关键词: Clinical; Genetic Determinism; Heart Atrium; Left; Magnetic Resonance Imaging; Molecular Genetics; Parents; Phenotype

R01 HL 144707: PARENT PROJECT SUMMARY/ABSTRACT Hispanics/Latinos (H/L) are the largest minority ethnic group in the US. Despite low socioeconomic status, H/L have lower mortality than non-Hispanic whites (NHW)-the "Hispanic Paradox." This survival advantage declines with time and generation, which has led to the proposition that erosion of healthful lifestyle habits and social resources combine with the cumulative stresses of immigration to degrade health. Longitudinal studies examining these factors are lacking. At the same time, there is evidence that the Hispanic Paradox may not apply to major diseases. H/L suffer a high burden of non-alcoholic fatty liver disease (NAFLD), including its more advanced form, non-alcoholic steatohepatitis (NASH), which is becoming the most common cause of liver transplant in the US. NASH has been difficult to study, however, because the diagnosis has depended on biopsy. While H/L also have a disproportionate burden of obesity and diabetes, this does not fully account for NAFLD. Meanwhile, discovery of two major genetic variants that interfere with hepatic lipid processing, but do not predispose to obesity or insulin resistance, has introduced the concept of "genetic NAFLD." This may be of particular relevance to H/L, because one such variant is highly prevalent in various H/L heritage groups. Unlike NAFLD, prevalence of CVD is lower in H/L than NHW, but cardiac dysfunction and heart failure risk appear higher. Data from our group using partial MRI of the liver has linked hepatic fibrosis to myocardial fibrosis. Here we will parlay the opportunity for a third exam of the Hispanic Community Health Study/Study of Latinos (SOL), and the strengths of contrast MRI, to address important knowledge gaps in this diverse group. We plan to evaluate relations of nativity and duration of US residence with MRI-determined hepatic fibrosis and myocardial strain, while leveraging longitudinal assessments of lifestyle, psychosocial and sociocultural factors to assess their cumulative impact on these phenotypes, and to explore mediation of immigration and acculturation effects. We will also examine the contributions of visceral fat and low adiponectin levels, as well as genetic susceptibility, alone and in combination, to hepatic fibrosis. Last, we will evaluate the association between hepatic fibrosis and myocardial fibrosis, along with proinflammatory and procoagulant factors that may link the two disorders. This study will yield key insights into the Hispanic Paradox in NAFLD and CVD and their behavioral and psychosocial determinants; newly characterize the burden of hepatic fibrosis in H/L and its genetic underpinnings; and investigate the liver-heart axis and underlying pathways as a potentially serious threat to the health of this vulnerable ethnic group.

R01 HL 144707：父项目摘要/摘要 西班牙裔/拉丁裔（H/L）是美国最大的少数民族群体。尽管社会经济地位较低，但H/L 比非西班牙裔白人（NHW）的死亡率低 - “西班牙裔悖论”。这种生存优势下降 随着时间和一代 资源与移民累积压力相结合，以降低健康。纵向研究 缺乏检查这些因素。同时，有证据表明西班牙裔悖论可能不会 适用于主要疾病。 H/L遭受非酒精性脂肪肝病（NAFLD）的高负担，包括更多 晚期形式，非酒精性脂肪性肝炎（NASH），这成为肝脏最常见的原因 在美国的移植。但是，纳什很难研究，因为诊断取决于活检。 尽管H/L的肥胖和糖尿病负担不成比例，但这并不能完全解释NAFLD。 同时，发现两种干扰肝脂质加工但不要 肥胖或胰岛素抵抗的易感性引入了“遗传NAFLD”的概念。这可能是 与H/L特别相关，因为在各种H/L遗产组中，这种变体非常普遍。与众不同 NAFLD，H/L的CVD患病率低于NHW，但心脏功能障碍和心力衰竭风险出现 更高。我们组的数据使用肝脏的部分MRI将肝纤维化与心肌纤维化联系起来。这里 我们将为西班牙裔社区健康研究/拉丁裔研究（SOL）的第三次考试提供机会 以及对比度MRI的优势，以解决这个多元化群体中重要的知识差距。我们计划 用MRI确定的肝纤维化和心肌评估美国住所的耶稣降生和持续时间的关系 应变，同时利用生活方式，社会心理和社会文化因素评估的纵向评估 它们对这些表型的累积影响，并探索移民和文化效应的中介。 我们还将研究内脏脂肪和低脂联素水平以及遗传易感性的贡献， 单独和结合使用肝纤维化。最后，我们将评估肝纤维化与 心肌纤维化，以及可能关联两种疾病的促炎和凝聚因子。这 研究将产生对NAFLD和CVD中西班牙裔悖论及其行为和社会心理的关键见解 决定因素；新来表征H/L及其遗传基础的肝纤维化负担；和 调查肝脏心脏轴和潜在的途径，以此作为对此健康的潜在严重威胁 脆弱的族裔群体。