Department of Pulmonary and Critical Care Medicine, Affiliated Xing Tai People Hospital of Hebei Medical University, Xingtai, China.
Department of Internal Medicine, Graduate School of Hebei North University, Zhangjiakou, China.
BMC Pulm Med. 2024 Sep 13;24(1):451. doi: 10.1186/s12890-024-03275-4.
Idiopathic pulmonary fibrosis (IPF) is a progressive and debilitating respiratory disease with a median survival of less than 5 years. In recent years, glutamine has been reported to be involved in the regulation of collagen deposition and cell proliferation in fibroblasts, thereby influencing the progression of IPF. However, the relationships between glutamine and the incidence, progression, and treatment response of IPF remain unclear. Our study aimed to investigate the relationship between circulating glutamine levels and IPF, as well as its potential as a therapeutic target.
We performed a comprehensive Mendelian Randomization (MR) analysis using the most recent genome-wide association study summary-level data. A total of 32 single nucleotide polymorphisms significantly correlated to glutamine levels were identified as instrumental variables. Eight MR analysis methods, including inverse variance weighted, MR-Egger, weighted median, weighted mode, constrained maximum likelihood, contamination mixture, robust adjusted profile score, and debiased inverse-variance weighted method, were used to assess the relationship between glutamine levels with IPF.
The inverse variance weighted analysis revealed a significant inverse correlation between glutamine levels and IPF risk (Odds Ratio = 0.750; 95% Confidence Interval : 0.592-0.951; P = 0.017). Sensitivity analyses, including MR-Egger regression and MR-PRESSO global test, confirmed the robustness of our findings, with no evidence of horizontal pleiotropy or heterogeneity.
Our study provides novel evidence for a causal relationship between lower circulating glutamine levels and increased risk of IPF. This finding may contribute to the early identification of high-risk individuals for IPF, disease monitoring, and development of targeted therapeutic strategies.
特发性肺纤维化（IPF）是一种进行性和使人虚弱的呼吸系统疾病，中位生存期不足 5 年。近年来，谷氨酰胺已被报道参与调节成纤维细胞中胶原蛋白的沉积和细胞增殖，从而影响 IPF 的进展。然而，谷氨酰胺与 IPF 的发病、进展和治疗反应之间的关系尚不清楚。我们的研究旨在探讨循环谷氨酰胺水平与 IPF 的关系及其作为治疗靶点的潜力。
我们使用最新的全基因组关联研究汇总水平数据进行了全面的孟德尔随机化（MR）分析。共鉴定出 32 个与谷氨酰胺水平显著相关的单核苷酸多态性作为工具变量。采用 8 种 MR 分析方法，包括逆方差加权法、MR-Egger 法、加权中位数法、加权众数法、约束最大似然法、污染混合物法、稳健调整轮廓评分法和无偏逆方差加权法，评估谷氨酰胺水平与 IPF 之间的关系。
逆方差加权分析显示，谷氨酰胺水平与 IPF 风险呈显著负相关（优势比=0.750；95%置信区间：0.592-0.951；P=0.017）。敏感性分析，包括 MR-Egger 回归和 MR-PRESSO 全局检验，证实了我们研究结果的稳健性，没有证据表明存在水平多效性或异质性。
本研究为循环谷氨酰胺水平较低与 IPF 风险增加之间存在因果关系提供了新的证据。这一发现可能有助于早期识别 IPF 的高危个体、疾病监测和开发靶向治疗策略。
