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

 描述（由申请人提供）：非酒精性脂肪性肝病（NAFLD）是最常见的肝病类型，也是代谢综合征的肝脏组成部分。据估计，根据种族/民族和诊断方式，它会影响17-33%的美国成年人口。已知的风险因素是胰岛素抵抗和肥胖，而促炎状态越来越多地被认为是一种新的风险因素。虽然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的某些组分联系起来。因此，已知引起全身炎症反应的因素可能代表了NAFLD发病机制中未被认识但可改变的途径。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起低度全身炎症的倾向。在实验动物和流行病学研究中已经证实了将升高的细胞因子水平与NAFLD联系起来的假设分子机制。CP最近与人类NAFLD有关，但该研究的效力不足。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）数据的二次数据分析来解决文献中的这一差距，该研究是一项针对东北部人群的前瞻性队列研究，该研究是一项基于人口的前瞻性队列研究。德国。SHIP研究是一项由4，308名参与者组成的具有良好特征的队列，这些参与者经历了高水平的腹部肥胖，代谢综合征和其他心脏代谢风险因素。将使用来自西班牙裔社区健康研究/拉丁美洲人研究的数据进行复制分析，其中n= 14，000名成年人测量了血清转氨酶和临床牙周状态。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。在这两个队列中，使用可比的方案来测量牙周袋深度和临床附着水平。在SHIP中，使用两个队列中的血清转氨酶水平和基线和随访时的肝脏超声来表征NAFLD。据报道，雌激素由于其抗氧化作用而对绝经前NAFLD的发生产生保护作用，因此我们假设在提出的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关联的修饰。

 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.