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Effect of l-arginine, asymmetric dimethylarginine, and symmetric dimethylarginine on ischemic heart disease risk: A Mendelian randomization study.

Abstract：

BACKGROUND:l-arginine is a commonly consumed dietary conditional essential amino acid found in food items and supplements, which is closely related to asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA). l-arginine is thought to increase nitric oxide and be cardioprotective, whereas ADMA and SDMA may inhibit nitric oxide synthesis and increase cardiovascular disease risk. Unexpectedly, l-arginine increased mortality in a small trial. To clarify the effects of these potential targets of intervention, we assessed the risk of ischemic heart disease (IHD) by genetically determined l-arginine, ADMA, and SDMA. METHODS:Single nucleotide polymorphisms (SNPs) contributing to l-arginine, ADMA, and SDMA, at genome-wide significance, were applied to the CARDIoGRAMplusC4D 1000 Genomes-based genome-wide association study IHD case (n=60,801, ~70% myocardial infarction)-control (n=123,504) study. We obtained unconfounded estimates using instrumental variable analysis by combining the Wald estimators for each SNP, taking into account any correlation between SNPs using weighted generalized linear regression. RESULTS:Higher l-arginine was associated with higher risk of IHD (odds ratio [OR] 1.18 per SD increase, 95% CI 1.03-1.36) and of myocardial infarction (OR 1.29, 95% CI 1.10-1.51), based on 2 SNPs from MED23. Symmetric dimethylarginine had an OR of 1.07 per SD (95% CI 0.99-1.17) for IHD based on 5 SNPs from AGXT2. Asymmetric dimethylarginine had and OR of 1.08 per SD (95% CI 0.99-1.19) for IHD based on 4 SNPs from DDAH1. CONCLUSION:l-arginine could possibly cause IHD. Given that l-arginine occurs in many common dietary items, investigation of its health effect is required.

journal_name

Am Heart J

journal_title

American heart journal

authors

Au Yeung SL,Lin SL,Lam HS,Schooling CM

doi

10.1016/j.ahj.2016.07.021

subject

Has Abstract

pub_date

2016-12-01 00:00:00

pages

54-61

eissn

0002-8703

issn

1097-6744

pii

S0002-8703(16)30165-X

journal_volume

182

pub_type

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