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。尽管社会经济地位低下，但H/L 他们的死亡率低于非西班牙裔白人(Nhw)--这就是“西班牙裔悖论”。这种生存优势正在减弱 随着时间和世代的推移，这导致了健康生活方式习惯和社会生活方式的侵蚀 资源与移民的累积压力相结合，会降低健康水平。纵向研究 目前还缺乏对这些因素的考察。与此同时，有证据表明，拉美裔悖论可能不会 适用于重大疾病。L患有高负担的非酒精性脂肪性肝病，包括其更多 晚期非酒精性脂肪性肝炎(NASH)，正成为肝脏最常见的原因 在美国进行移植。然而，NASH的研究一直很困难，因为诊断依赖于活检。 虽然H/L也有不成比例的肥胖和糖尿病负担，但这并不能完全解释非酒精性脂肪肝。 同时，发现了两个主要的基因变异，它们干扰了肝脏的脂肪加工，但没有 易患肥胖症或胰岛素抵抗的人提出了“遗传性NAFLD”的概念。这可能是 与H/L特别相关，因为一个这样的变体在各种H/L遗产群体中非常普遍。不像 在非酒精性脂肪肝中，H/L组的心血管疾病患病率低于NHW组，但出现心功能不全和心力衰竭危险。 再高一点。我们小组使用部分肝脏核磁共振成像的数据将肝纤维化与心肌纤维化联系起来。这里 我们将利用西班牙裔社区健康研究/拉美裔研究(SOL)第三次考试的机会， 以及对比磁共振成像的优势，以解决这一多样化群体中的重要知识差距。我们计划 评估出生在美国和在美国居住的时间与MRI确定的肝纤维化和心肌梗死的关系 压力，同时利用对生活方式、心理社会和社会文化因素的纵向评估来评估 他们对这些表型的累积影响，并探索移民和文化适应的中介效应。 我们还将研究内脏脂肪和低脂联素水平的贡献，以及遗传易感性， 单独和联合使用，都会导致肝纤维化。最后，我们将评估肝纤维化与 心肌纤维化，以及可能将这两种疾病联系在一起的促炎和促凝因子。这 研究将对NAFLD和CVD的西班牙裔悖论及其行为和心理社会产生关键见解 决定因素；H/L的肝纤维化负担及其遗传基础的新特征；以及 调查肝脏-心轴和潜在的通路，认为这是对健康的潜在严重威胁 易受伤害的族群。