Lee Yura, Chen Han, Chen Wei, Qi Qibin, Afshar Majid, Cai Jianwen, Daviglus Martha L, Thyagarajan Bharat, North Kari E, London Stephanie J, Boerwinkle Eric, Celedón Juan C, Kaplan Robert C, Yu Bing
Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15224, USA.
Metabolites. 2022 Apr 16;12(4):359. doi: 10.3390/metabo12040359.
Asthma disproportionally affects Hispanic and/or Latino backgrounds; however, the relation between circulating metabolites and asthma remains unclear. We conducted a cross-sectional study associating 640 individual serum metabolites, as well as twelve metabolite modules, with asthma in 3347 Hispanic/Latino background participants (514 asthmatics, 15.36%) from the Hispanic/Latino Community Health Study/Study of Latinos. Using survey logistic regression, per standard deviation (SD) increase in 1-arachidonoyl-GPA (20:4) was significantly associated with 32% high odds of asthma after accounting for clinical risk factors (p = 6.27 × 10−5), and per SD of the green module, constructed using weighted gene co-expression network, was suggestively associated with 25% high odds of asthma (p = 0.006). In the stratified analyses by sex and Hispanic and/or Latino backgrounds, the effect of 1-arachidonoyl-GPA (20:4) and the green module was predominantly observed in women (OR = 1.24 and 1.37, p < 0.001) and people of Cuban and Puerto-Rican backgrounds (OR = 1.25 and 1.27, p < 0.01). Mutations in Fatty Acid Desaturase 2 (FADS2) affected the levels of 1-arachidonoyl-GPA (20:4), and Mendelian Randomization analyses revealed that high genetically regulated 1-arachidonoyl-GPA (20:4) levels were associated with increased odds of asthma (p < 0.001). The findings reinforce a molecular basis for asthma etiology, and the potential causal effect of 1-arachidonoyl-GPA (20:4) on asthma provides an opportunity for future intervention.
哮喘对西班牙裔和/或拉丁裔背景人群的影响尤为严重；然而，循环代谢物与哮喘之间的关系仍不明确。我们开展了一项横断面研究，在西班牙裔/拉丁裔社区健康研究/拉丁裔研究的3347名西班牙裔/拉丁裔背景参与者（514名哮喘患者，占15.36%）中，将640种个体血清代谢物以及12个代谢物模块与哮喘进行关联分析。采用调查逻辑回归分析，在考虑临床风险因素后，1-花生四烯酰-GPA（20:4）每增加一个标准差（SD），哮喘高发病几率显著增加32%（p = 6.27 × 10−5），使用加权基因共表达网络构建的绿色模块每增加一个SD，哮喘高发病几率提示性增加25%（p = 0.006）。在按性别和西班牙裔和/或拉丁裔背景进行的分层分析中，1-花生四烯酰-GPA（20:4）和绿色模块的影响主要在女性（OR = 1.24和1.37，p < 0.001）以及古巴和波多黎各背景人群中观察到（OR = 1.25和1.27，p < 0.01）。脂肪酸去饱和酶2（FADS2）的突变影响了1-花生四烯酰-GPA（20:4）的水平，孟德尔随机化分析表明，遗传调控的1-花生四烯酰-GPA（20:4）高水平与哮喘发病几率增加相关（p < 0.001）。这些发现强化了哮喘病因的分子基础，1-花生四烯酰-GPA（20:4）对哮喘的潜在因果效应为未来的干预提供了机会。
