Department of Gastroenterology, The First Hospital of China Medical University, Shenyang, China.
School of Health Management, China Medical University, Shenyang, China.
Eur J Nutr. 2024 Dec;63(8):3075-3091. doi: 10.1007/s00394-024-03491-y. Epub 2024 Sep 6.
BACKGROUND: Growing studies have indicated an association between dietary factors and gastroesophageal reflux disease (GERD). However, whether these associations refer to a causal relationship and the potential mechanism by which dietary factors affect GERD is still unclear. METHODS: A two-step mendelian randomization analysis was performed to obtain causal estimates of dietary factors, blood lipids on GERD. Independent genetic variants associated with 13 kinds of dietary factors and 5 kinds of blood lipids at the genome-wide significance level were selected as instrumental variables. The summary statistics for GERD were obtained from European Bioinformatics Institute, including 129,080 cases and 473,524 controls. Inverse variance weighted was utilized as the main statistical method. MR-Egger intercept test, Cochran's Q test, and leave-one-out analysis were performed to evaluate possible heterogeneity and pleiotropy. And the potential reverse causality was assessed using Steiger filtering. RESULTS: The results of the inverse variance weighted method indicated that genetically predicted total pork intake (OR = 2.60, 95% CI: 1.21-5.58, p = 0.0143), total bread intake (OR = 0.68, 95% CI: 0.46-0.99, p = 0.0497), total cereal intake (OR = 0.42, 95% CI: 0.31-0.56, p = 2.98E-06), and total cheese intake (OR = 0.41, 95% CI: 0.27-0.61, p = 1.06E-05) were associated with the risk of GERD. Multivariable Mendelian randomization analysis also revealed a negative association between total cereal intake, total cheese intake and the risk of GERD, but the effect of total pork intake and total bread intake on GERD disappeared after adjustment of smoking, alcohol consumption, use of calcium channel blockers, BMI, physical activity levels, and biological sex (age adjusted). Furthermore, the concentration of low-density lipoprotein cholesterol (LDL-C) is negatively correlated with total cheese intake, which mediates the impact of total cheese intake on GERD. The proportion mediated by LDL-C is 2.27% (95%CI: 1.57%, 4.09%). CONCLUSIONS: This study provides evidence that an increase in total cereal intake and total cheese intake will decrease the risk of GERD. Additionally, LDL-C mediates the causal effect of total cheese intake on GERD. These results provide new insights into the role of dietary factors and blood lipids in GERD, which is beneficial for disease prevention.
背景：越来越多的研究表明，饮食因素与胃食管反流病（GERD）之间存在关联。然而，这些关联是否指向因果关系，以及饮食因素影响 GERD 的潜在机制尚不清楚。
方法：采用两步孟德尔随机化分析来获得与饮食因素、血脂与 GERD 相关的因果估计值。选择全基因组显著水平与 13 种饮食因素和 5 种血脂相关的独立遗传变异作为工具变量。通过全基因组关联研究（GWAS）获取 GERD 的汇总统计数据，包括 129080 例病例和 473524 例对照。采用逆方差加权法作为主要统计方法。采用 MR-Egger 截距检验、Cochran's Q 检验和逐一排除分析来评估可能存在的异质性和多效性。采用 Steiger 过滤法评估潜在的反向因果关系。
结果：逆方差加权法的结果表明，遗传预测的总猪肉摄入量（OR=2.60，95%CI：1.21-5.58，p=0.0143）、总面包摄入量（OR=0.68，95%CI：0.46-0.99，p=0.0497）、总谷物摄入量（OR=0.42，95%CI：0.31-0.56，p=2.98E-06）和总奶酪摄入量（OR=0.41，95%CI：0.27-0.61，p=1.06E-05）与 GERD 的风险相关。多变量孟德尔随机化分析还显示，总谷物摄入量和总奶酪摄入量与 GERD 的风险呈负相关，但在调整吸烟、饮酒、使用钙通道阻滞剂、BMI、体力活动水平和性别（年龄调整后）后，总猪肉摄入量和总面包摄入量对 GERD 的影响消失了。此外，低密度脂蛋白胆固醇（LDL-C）浓度与总奶酪摄入量呈负相关，LDL-C 介导了总奶酪摄入量对 GERD 的影响。LDL-C 介导的比例为 2.27%（95%CI：1.57%，4.09%）。
结论：本研究提供了证据表明，增加总谷物摄入量和总奶酪摄入量会降低 GERD 的风险。此外，LDL-C 介导了总奶酪摄入量对 GERD 的因果效应。这些结果为饮食因素和血脂在 GERD 中的作用提供了新的见解，有助于疾病预防。
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