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: 9111407
• 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/9111407
• 关键词: Address; Adult; Affect; Alcohols; Animals; Antioxidants; Attention; CCL2 gene; Central obesity; Chronic; Cirrhosis; Clinical; Cohort Studies; Data; Data Analyses; Data Sources; Diagnostic; Disease; Enzymes; Epidemiologic Studies; Estrogens; Ethnic Origin; Etiology; Experimental Animal Model; 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; Protocols documentation; Race; Reporting; Risk; Risk Factors; Serum; Structural Models; Study of Latinos; Tooth Loss; Transaminases; Ultrasonography; Uncertainty; Validation; Variant; Viral hepatitis; Weight; Woman; base; cardiometabolic risk; cohort; cytokine; experience; follow-up; gender difference; liver function; men; modifiable risk; mortality; non-alcoholic fatty liver; nonalcoholic steatohepatitis; phenotypic data; population based; prospective; protective effect; public health relevance; response; 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（由适用提供）：非酒精性脂肪肝病（NAFLD）是最常见的肝病类型，也是代谢综合征的肝成分。据估计，根据种族/种族和诊断方式，它会影响17-33％的美国人口。已知的危险因素是胰岛素抵抗和肥胖，而促炎状态越来越被认为是新兴的危险因素。但是，NAFLD的发病机理知之甚少，流行病学研究已将促炎细胞因子与代谢综合征和NAFLD的某些成分联系起来。这是，已知引起全身性炎症反应的已知因素可能代表了NAFLD疗法发生中未识别但可修改的途径。具体而言，慢性牙周炎（CP）是牙齿脱落的主要原因，影响了大约45％的美国人群，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引起低度全身性炎症细胞因子的希望。在实验动物和流行病学研究中已经证明了将升高细胞因子水平与NAFLD联系起来的假设的分子机制。 CP最近与人类的NAFLD联系在一起，但该研究的动力不足。由于NAFLD患病率的不确定性以及对其与CP关系的知识有限，我们建议通过对波美那能健康研究（Ship）的数据分析来解决文献中的这一差距，这是一项基于人群的前瞻性人群，对德国东北部的前瞻性队列研究。造船研究是一个良好的人群，由4,308名参与者组成，他们经历了高水平的腹部肥胖，代谢综合征和其他心脏代谢危险因素。将使用来自西班牙裔社区健康研究/拉丁裔研究的数据进行复制分析，其中n = 14,000名成年人对血清转氨酶和临床牙周地位进行了测量。 CP和NAFLD之间的关系将在同时进行横截面和纵向研究。在这两个队列中，都使用可比较的方案来测量牙周口袋深度和临床依恋水平。 NAFLD在两个队列中使用串行转氨酶水平以及基线时的肝超声和肝脏的随访对NAFLD进行了表征。据报道，雌激素由于其抗氧化作用而对NAFLD产生保护作用，因此在拟议的CP/NAFLD关联中假设性别差异。最后，由于CP和NAFLD的炎症基础，我们进一步建议通过一系列通用炎症标记来评估CP/NAFLD关联的修改。