Plasma metabolites and risk of myocardial infarction:a bidir-ectional Mendelian randomization study
Dong-Hua LI1
Qiang WU2
Jing-Sheng LAN1
Shuo CHEN3
You-Yi HUANG1
Lan-Jin WU1
Zhi-Qing QIN1
Ying HUANG1
Wan-Zhong HUANG4
Ting ZENG4
Xin HAO5
Hua-Bin SU4
Qiang SU4
1.Department of Cardiovascular Medicine,Minzu Hospital of Guangxi Zhuang Autonomous Region,Guangxi,China2.Senior Department of Cardiology,the Sixth Medical Center,Chinese PLA General Hospital,Beijing,China3.Library of Graduate School,Chinese PLA General Hospital,Beijing,China4.Department of Cardiology,Jiangbin Hospital of Gu-angxi Zhuang Autonomous Region,Guangxi,China5.Health Management Institute,the Second Medical Center,Chin-ese PLA General Hospital,Beijing,China
摘要：BACKGROUND Myocardial infarction(MI)is a critical cardiovascular event with multifaceted etiology,involving several ge-netic and environmental factors.It is essential to understand the function of plasma metabolites in the development of MI and un-ravel its complex pathogenesis.
METHODS This study employed a bidirectional Mendelian randomization(MR)approach to investigate the causal relations-hips between plasma metabolites and MI risk.We used genetic instruments as proxies for plasma metabolites and MI and con-ducted MR analyses in both directions to assess the impact of metabolites on MI risk and vice versa.In addition,the large-scale genome-wide association studies datasets was used to identify genetic variants associated with plasma metabolite(1400 metabol-ites)and MI(20,917 individuals with MI and 440,906 individuals without MI)susceptibility.Inverse variance weighted was the primary method for estimating causal effects.MR estimates are expressed as beta coefficients or odds ratio(OR)with 95%CI.
RESULTS We identified 14 plasma metabolites associated with the occurrence of MI(P＜0.05),among which 8 plasma metab-olites[propionylglycine levels(OR = 0.922,95%CI:0.881-0.965,P＜0.001),gamma-glutamylglycine levels(OR = 0.903,95%CI:0.861-0.948,P＜0.001),hexadecanedioate(C16-DC)levels(OR = 0.941,95%CI:0.911-0.973,P＜0.001),pentose acid levels(OR = 0.923,95%CI:0.877-0.972,P = 0.002),X-24546 levels(OR = 0.936,95%CI:0.902-0.971,P＜0.001),glycine levels(OR = 0.936,95%CI:0.909-0.964,P＜0.001),glycine to serine ratio(OR = 0.930,95%CI:0.888-0.974,P = 0.002),and mannose to trans-4-hydroxyproline ratio(OR = 0.912,95%CI:0.869-0.958,P＜0.001)]were correlated with a decreased risk of MI,whereas the remaining 6 plasma meta-bolites[1-palmitoyl-2-arachidonoyl-GPE(16:0/20:4)levels(OR = 1.051,95%CI:1.018-1.084,P = 0.002),behenoyl dihydrosphin-gomyelin(d18:0/22:0)levels(OR = 1.076,95%CI:1.027-1.128,P = 0.002),1-stearoyl-2-docosahexaenoyl-GPE(18:0/22:6)levels(OR = 1.067,95%CI:1.027-1.109,P = 0.001),alpha-ketobutyrate levels(OR = 1.108,95%CI:1.041-1.180,P = 0.001),5-acetylamino-6-formylamino-3-methyluracil levels(OR = 1.047,95%CI:1.019-1.076,P＜0.001),and N-acetylputrescine to(N(1)+ N(8))-acetyl-spermidine ratio(OR = 1.045,95%CI:1.018-1.073,P＜0.001)]were associated with an increased risk of MI.Furthermore,we also observed that the mentioned relationships were unaffected by horizontal pleiotropy(P＞0.05).On the contrary,MI did not lead to significant alterations in the levels of the aforementioned 14 plasma metabolites(P＞0.05 for each comparison).
CONCLUSIONS Our bidirectional MR study identified 14 plasma metabolites associated with the occurrence of MI,among wh-ich 13 plasma metabolites have not been reported previously.These findings provide valuable insights for the early diagnosis of MI and potential therapeutic targets.
机标关键词：plasmastudyriskbidir-ectionalinfarctionmendelianmetabolitesmyocardial
论文发表日期：2024-02-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：13( 219-231 )