背景:越来越多的证据表明谷氨酰胺水平与胃肠道疾病的风险有关,然而,因果关系的存在仍然不确定。在这项研究中,我们采用孟德尔随机化(MR)方法来调查谷氨酰胺和结肠炎之间的潜在因果关系,炎症性肠病(IBD),和消化道肿瘤。方法:从涉及114,751名参与者的全基因组关联研究(GWAS)中确定了谷氨酰胺暴露的遗传工具变量。我们汇集了欧洲人群胃肠道疾病的GWAS统计数据,包括结肠炎(病例=1193,对照=461,740),IBD(病例=31,665,对照=33,977),克罗恩病(病例=17,897,对照组=33,977),溃疡性结肠炎(病例=1,239,对照=990),食管癌(病例=740,对照=372,016),胃癌(病例=6,563,对照=195,745),肝细胞癌(病例=168,对照=372,016),肝胆管癌(病例=418,对照=159,201),胰腺癌(病例=1,196,对照=475,049),和结肠癌(病例=1,494,对照=461,439)。为了确保我们发现的有效性,我们利用了几种分析方法,包括逆方差加权,加权中位数,加权模式,MR-Egger,和简单的模式方法。结果:使用IVW方法,我们发现谷氨酰胺水平与结肠癌呈负相关(OR=0.998;95%CI:0.997-1.000;P=0.027),结肠炎(OR=0.998;95%CI:0.997-1.000;P=0.020),和IBD(OR=0.551;95%CI:0.343-0.886;P=0.014)。亚组分析显示谷氨酰胺与克罗恩病呈负相关(OR=0.375;95%CI:0.253-0.557;P=1.11E-06),但不与溃疡性结肠炎(OR=0.508;95%CI:0.163-1.586;P=0.244)。谷氨酰胺水平与食管癌无显著相关性(OR=1.000;95%CI:0.999-1.001;P=0.566),胃癌(OR=0.966;95%CI:0.832-1.121;P=0.648),肝细胞癌(OR=1.000;95%CI:0.999-1.000;P=0.397),肝胆管癌(OR=0.819;95%CI:0.499-1.344;P=0.430),和胰腺癌(OR=1.130;95%CI:0.897-1.423;P=0.301)。敏感性分析也支持这一发现,肯定了我们研究的可靠性和稳健性。结论:这项研究表明,欧洲人群的血液谷氨酰胺水平可能会降低结肠癌的风险,结肠炎,IBD,特别是克罗恩病。然而,为了证实这种因果关系,必须进行涉及不同祖先的其他研究。
Backgrounds: There is growing evidence linking glutamine levels to the risk of gastrointestinal diseases, yet the presence of a causal relationship remains uncertain. In this
study, we employed a Mendelian randomization (MR) approach to investigate potential causal associations between glutamine and colitis, inflammatory bowel disease (
IBD), and digestive tumors. Methods: Genetic instrumental variables for glutamine exposure were identified from a genome-wide association
study (GWAS) involving 114,751 participants. We pooled statistics from GWAS of gastrointestinal diseases in European populations, encompassing colitis (cases=1193, controls=461,740), IBD (cases=31,665, controls=33,977), Crohn\'s disease (cases=17,897, controls=33,977), ulcerative colitis (cases=1,239, controls=990), oesophageal cancer (cases=740, controls=372,016), gastric cancer (cases=6,563, controls=195,745), liver cell carcinoma (cases=168, controls=372,016), hepatic bile duct cancer (cases=418, controls=159,201), pancreatic cancer (cases=1,196, controls=475,049), and colon cancer (cases=1,494, controls=461,439). To ensure the validity of our findings, we utilized several analytical approaches including inverse variance weighted, weighted median, weighted mode, MR-Egger, and simple mode method. Results: Using the IVW method, we found that glutamine levels were inversely associated with colon cancer (OR = 0.998; 95% CI: 0.997-1.000; P = 0.027), colitis (OR = 0.998; 95% CI: 0.997-1.000; P = 0.020), and
IBD (OR = 0.551; 95% CI: 0.343-0.886; P = 0.014). Subgroup analysis revealed a negative association between glutamine and Crohn\'s disease (OR = 0.375; 95% CI: 0.253-0.557; P = 1.11E-06), but not with ulcerative colitis (OR = 0.508; 95% CI: 0.163-1.586; P = 0.244). Glutamine levels showed no significant correlation with oesophageal cancer (OR = 1.000; 95% CI: 0.999-1.001; P = 0.566), gastric cancer (OR = 0.966; 95% CI: 0.832-1.121; P = 0.648), liver cell carcinoma (OR = 1.000; 95% CI: 0.999-1.000; P = 0.397), hepatic bile duct cancer (OR = 0.819; 95% CI: 0.499-1.344; P = 0.430), and pancreatic cancer (OR = 1.130; 95% CI: 0.897-1.423; P = 0.301). Sensitivity analyses also supports this finding, affirming the reliability and robustness of our study. Conclusions: This study suggests that blood glutamine levels in European populations may lower the risk of colon cancer, colitis, and
IBD, particularly Crohn\'s disease. Nevertheless, additional research involving a diverse range of ancestries is imperative to corroborate this causal relationship.