Zhang Xin, Cai Yuying, Jiang Yaping, Du Wei, An Weishu, Fu Qiangqiang, Chen Yihui
Department of Ophthalmology, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, China.
Department of Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Mol Biosci. 2024 Mar 21;11:1368669. doi: 10.3389/fmolb.2024.1368669. eCollection 2024.
Lipid metabolism disorders were observationally associated with chalazion, but the causality of the related circulating metabolites on chalazion remained unknown. Here, we investigated the potential causal relationship between circulating metabolites and chalazion using two-sample Mendelian randomization (MR) analysis. For the primary analysis, 249 metabolic biomarkers were obtained from the UK Biobank, and 123 circulating metabolites were obtained from the publication by Kuttunen et al. for the secondary analysis. Chalazion summary data were obtained from the FinnGen database. Inverse variance weighted (IVW) is the main MR analysis method, and the MR assumptions were evaluated in sensitivity and colocalization analyses. Two MR analyses results showed that the common metabolite, alanine, exhibited a genetic protective effect against chalazion (primary analysis: odds ratio [OR] = 0.680; 95% confidence interval [CI], 0.507-0.912; = 0.010; secondary analysis: OR = 0.578; 95% CI, 0.439-0.759; = 0.00008). The robustness of the findings was supported by heterogeneity and horizontal pleiotropy analysis. Two colocalization analyses showed that alanine did not share a region of genetic variation with chalazion (primary analysis: PPH = 1.95%; secondary analysis: PPH = 25.3%). Moreover, previous studies have suggested that an increase in the degree of unsaturation is associated with an elevated risk of chalazion (OR = 1.216; 95% CI, 1.055-1.401; = 0.007), with omega-3 fatty acids (OR = 1.204; 95% CI, 1.054-1.377; = 0.006) appearing to be the major contributing factor, as opposed to omega-6 fatty acids (OR = 0.850; 95% CI, 0.735-0.982; = 0.027). This study suggests that alanine and several unsaturated fatty acids are candidate molecules for mechanistic exploration and drug target selection in chalazion.
脂质代谢紊乱在观察上与睑板腺囊肿有关，但相关循环代谢物对睑板腺囊肿的因果关系尚不清楚。在此，我们使用两样本孟德尔随机化（MR）分析研究了循环代谢物与睑板腺囊肿之间的潜在因果关系。在主要分析中，从英国生物银行获得了249种代谢生物标志物，在次要分析中，从Kuttunen等人的出版物中获得了123种循环代谢物。睑板腺囊肿汇总数据来自芬兰基因数据库。逆方差加权（IVW）是主要的MR分析方法，并在敏感性和共定位分析中评估了MR假设。两项MR分析结果表明，常见代谢物丙氨酸对睑板腺囊肿具有遗传保护作用（主要分析：比值比[OR]=0.680；95%置信区间[CI]，0.507-0.912；P=0.010；次要分析：OR=0.578；95%CI，0.439-0.759；P=0.00008）。异质性和水平多效性分析支持了研究结果的稳健性。两项共定位分析表明，丙氨酸与睑板腺囊肿没有共享遗传变异区域（主要分析：PPH=1.95%；次要分析：PPH=25.3%）。此外，先前的研究表明，不饱和度的增加与睑板腺囊肿风险升高有关（OR=1.216；95%CI，1.055-1.401；P=0.007），其中ω-3脂肪酸（OR=1.204；95%CI，1.054-1.377；P=0.006）似乎是主要促成因素，而ω-6脂肪酸则相反（OR=0.850；95%CI，0.735-0.982；P=0.027）。这项研究表明，丙氨酸和几种不饱和脂肪酸是睑板腺囊肿机制探索和药物靶点选择的候选分子。
