Is Periodontal Disease Involved in the Etiology of Non-Alcoholic Fatty Liver Disease

牙周病是否与非酒精性脂肪肝的病因有关

• 批准号: 9233074
• 负责人: Gary Douglas Slade
• 金额: $ 15.2万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-01 至 2018-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9233074
• 关键词: Address; Adult; Affect; Alcohols; Animals; Antioxidants; Attention; CCL2 gene; Central obesity; Chronic; Cirrhosis; Clinical; Data; Data Analyses; Data Sources; Diagnostic; Disease; Enzymes; Estrogens; Ethnic Origin; Etiology; Experimental Animal Model; Follow-Up Studies; Gender; Gene Targeting; Genes; Genetic; Genetic Markers; Genotype; German population; Germany; Health; Health Care Costs; Hemochromatosis; Hemorrhage; Hepatic; Hispanic Community Health Study/Study of Latinos; Homeostasis; Human; Infection; Inflammation; Inflammatory; Inflammatory Response; Insulin Resistance; Interleukin-6; Knowledge; Link; Literature; Liver; Liver diseases; Measurement; Measures; Mediating; Metabolic syndrome; Modality; Modeling; Modification; Molecular; Obesity; Oral Examination; Participant; Pathogenesis; Pathway interactions; Periodontal Diseases; Periodontal Pocket; Periodontitis; Pharmaceutical Preparations; Population; Postmenopause; Premenopause; Prevalence; Primary carcinoma of the liver cells; Probability; Prospective cohort study; Protocols documentation; Race; Reporting; Risk; Risk Factors; Serum; Structural Models; Tooth Loss; Transaminases; Ultrasonography; Uncertainty; Validation; Variant; Viral hepatitis; Woman; base; cardiometabolic risk; cohort; cytokine; epidemiology study; experience; follow-up; gender difference; inflammatory marker; liver function; men; modifiable risk; mortality; non-alcoholic fatty liver; nonalcoholic steatohepatitis; phenotypic data; population based; protective effect; public health relevance; response; secondary analysis; trait

 DESCRIPTION (provided by applicant): Non-alcoholic fatty liver disease (NAFLD) is the most common type of liver disease and the hepatic component of the metabolic syndrome. It is estimated to affect 17-33% of the adult U.S. population depending on race/ethnicity and diagnostic modality. Known risk factors are insulin resistance and obesity while proinflammatory state is increasingly recognized as an emerging risk factor. Though, the pathogenesis of NAFLD is poorly understood, epidemiologic studies have linked proinflammatory cytokines to certain components of the metabolic syndrome and NAFLD. Thus, factors known to elicit a systemic inflammatory response potentially represent an unrecognized but modifiable pathway in NAFLD etiopathogenesis. Specifically, chronic periodontitis (CP), a major cause of tooth loss, affects approximately 45% of the adult U.S. population and is reported to exacerbate insulin resistance. Additionally, animal and epidemiologic studies have reported the propensity for CP to elicit low-grade systemic inflammation via proinflammatory cytokines. The hypothesized molecular mechanism linking elevated cytokine levels to NAFLD has been demonstrated in experimental animal and epidemiologic studies. CP was recently linked to NAFLD in humans but the study was insufficiently powered. Due to uncertainty in prevalence of NAFLD and limited knowledge regarding its relation with CP, we propose to address this gap in literature through a secondary data analysis of data from the Study of Health in Pomerania (SHIP), a population based prospective cohort study of northeastern Germany. SHIP study is a well-characterized cohort of 4,308 participants who experience high levels of abdominal obesity, metabolic syndrome, and other cardio-metabolic risk factors. Replication analysis will be conducted using data from the Hispanic Community Health Study/Study of Latinos in which n=14,000 adults had measurements of serum transaminases and clinical periodontal status. Relationships between CP and NAFLD will be investigated cross-sectionally in both cohorts and longitudinally in SHIP. In both cohorts, comparable protocols were used to measure of periodontal pocket depth and clinical attachment level. NAFLD was characterized using serum transaminase levels in both cohorts and with hepatic ultrasound at baseline and follow-up in SHIP. Estrogens are reported to exert protective effects against NAFLD occurrence among premenopausal because of its antioxidant effects, thus we hypothesize a gender difference in the proposed CP/NAFLD association. Lastly, because of the inflammatory basis of CP and NAFLD, we further propose to assess modification of the CP/NAFLD association by a panel of genetic markers of inflammation.

 描述（由申请人提供）：非酒精性脂肪肝病（NAFLD）是最常见的肝脏疾病类型，也是代谢综合征的肝脏组成部分。据估计，它会影响 17-33% 的美国成年人口，具体取决于种族/民族和诊断方式。已知的危险因素是胰岛素抵抗和肥胖，而促炎症状态越来越被认为是一个新兴的危险因素。尽管人们对 NAFLD 的发病机制知之甚少，但流行病学研究已将促炎细胞因子与代谢综合征和 NAFLD 的某些组成部分联系起来。因此，已知引起全身炎症反应的因素可能代表 NAFLD 发病机制中一条未被识别但可改变的途径。具体而言，慢性牙周炎 (CP) 是牙齿脱落的主要原因，影响着大约 45% 的美国成年人口，据报道会加剧胰岛素抵抗。此外，动物和流行病学研究报告了 CP 通过促炎细胞因子引发低度全身炎症的倾向。实验动物和流行病学研究已经证明了将细胞因子水平升高与 NAFLD 联系起来的假设分子机制。最近发现 CP 与人类 NAFLD 有关，但该研究的证据不足。由于 NAFLD 患病率的不确定性以及对其与 CP 关系的了解有限，我们建议通过对波美拉尼亚健康研究 (SHIP)（德国东北部一项基于人群的前瞻性队列研究）的数据进行二次数据分析来解决文献中的这一空白。 SHIP 研究是一个由 4,308 名参与者组成的特征明确的队列，他们患有高水平的腹部肥胖、代谢综合征和其他心脏代谢危险因素。将使用西班牙社区健康研究/拉丁裔研究的数据进行复制分析，其中 n=14,000 名成年人进行了血清转氨酶和临床牙周状态的测量。 CP 和 NAFLD 之间的关系将在两个队列中进行横断面研究，并在 SHIP 中进行纵向研究。在两个队列中，使用类似的方案来测量牙周袋深度和临床附着水平。使用两个队列中的血清转氨酶水平以及 SHIP 中基线和随访时的肝脏超声来表征 NAFLD。据报道，雌激素因其抗氧化作用而对绝经前 NAFLD 的发生发挥保护作用，因此我们假设所提出的 CP/NAFLD 关联中存在性别差异。最后，由于 CP 和 NAFLD 的炎症基础，我们进一步建议通过一组炎症遗传标记来评估 CP/NAFLD 关联的修改。