东亚地区胃食管反流病流行趋势及多维度病因

Epidemiologic Trends and Multidimensional Etiology of Gastroesophageal Reflux Disease in East Asia

摘要: 目的：基于2021年全球疾病负担(Global Burden of Disease, GBD)数据库及两样本孟德尔随机化(Mendelian Randomization, MR)方法，分析近30年全球及东亚各国胃食管反流病(Gastroesophageal Reflux Disease, GERD)的疾病负担及潜在危险因素。方法：整理GBD 2021中近30年全球和东亚各胃食管反流病的发病、患病与伤残调整寿命年(Disability-Adjusted Life Years, DALYs)绝对值，并获取相应的年龄标准化率(Age-Standardized Rate, ASR)。从全基因组关联研究(Genome-Wide Association Studies, GWAS)获取暴露及结局数据，主要采取逆方差加权(Inverse-Variance Weighted, IVW)方法分析因果。结果：1990~2021年，全球和东亚GERD发病、患病绝对数均上升，但东亚地区DALYS小幅下降。蒙古国疾病负担最重且增长最快，中国绝对患病数最高。MR结果显示：手机使用时长(OR = 1.42, P < 0.01)、C反应蛋白(OR = 1.42, P < 0.01)、舒张压(OR = 1.14, P < 0.01)、体重指数(OR = 1.13, P < 0.01)、Catenibacterium菌属(OR = 1.09, P < 0.05)、Allisonella菌属(OR = 1.07, P = 0.007)、甘油三酯(OR = 1.06, P < 0.05)都与GERD风险增加显著相关。载脂蛋白A-1 (OR = 0.94, P < 0.05)、Prevotella7菌属(OR = 0.94, P = 0.003)、Ruminococcus菌属(OR = 0.87, P = 0.03)、家庭收入(OR = 0.64, P < 0.001)和受教育程度(OR = 0.30, P < 0.001)具有保护作用。结论：尽管东亚地区GERD的年龄标准化负担总体呈下降趋势，但绝对患病人数显著上升，各国间差异明显。MR分析提示代谢、行为及肠道菌群等多维因素可能与GERD存在因果关系，但因分析主要基于欧洲人群数据，其在东亚人群中的适用性尚需进一步验证。未来应结合本土数据开展验证性研究，并针对代谢与微生态因素探索分层防控策略。

Abstract: Objective: Using the Global Burden of Disease (GBD) 2021 database and two-sample Mendelian Randomization (MR), we analyzed the disease burden and potential risk factors of Gastroesophageal Reflux Disease (GERD) burden worldwide and across East Asian countries over the past 30 years. Methods: From GBD 2021, we obtained annual incident cases, prevalent cases, and absolute values of Disability-Adjusted Life Years (DALYs) for GERD worldwide and across East Asian countries over the past 30 years, and calculated the corresponding Age-Standardized Rates (ASRs). Exposure and outcome data were obtained from Genome-Wide Association Study (GWAS), and causal analysis was primarily conducted using the Inverse-Variance Weighted (IVW) method. Results: Between 1990 and 2021, absolute numbers of GERD incidence and prevalence increased both globally and within East Asia, whereas East Asia showed a slight decline in DALY ASR. Mongolia carried the highest and fastest-rising burden, while China had the largest absolute number of prevalent cases. MR identified several risk-increasing exposures: longer smartphone use duration (OR = 1.42, P < 0.01), C-reactive protein (OR = 1.42, P < 0.01), diastolic blood pressure (OR = 1.14, P < 0.01), body-mass index (OR = 1.13, P < 0.01), Catenibacterium (OR = 1.09, P < 0.05), Allisonella (OR = 1.07, P = 0.007), and triglycerides (OR = 1.06, P < 0.05). Protective associations were observed for apolipoprotein A-1 (OR = 0.94, P < 0.05), Prevotella7 (OR = 0.94, P = 0.003), Ruminococcus (OR = 0.87, P = 0.03), household income (OR = 0.64, P < 0.001), and educational attainment (OR = 0.30, P < 0.001). Conclusions: Although the age-standardized burden of GERD in East Asia has shown a modest decline, the absolute number of cases has increased substantially with marked heterogeneity across countries. MR analyses suggest potential causal associations with metabolic, behavioral, and gut microbiota factors; however, these findings are primarily derived from European populations data and require further validation in East Asian populations. Stratified prevention strategies should consider metabolic and microbiome-related targets, pending confirmation from region-specific studies.