Methylenetetrahydrofolate Dehydrogenase 1 Polymorphisms Modify the Associations of Plasma Glycine and Serine With Risk of Acute Myocardial Infarction in Patients With Stable Angina Pectoris in WENBIT (Western Norway B Vitamin Intervention Trial)

Q Medicine

Circulation-Cardiovascular Genetics Pub Date : 2016-11-21 DOI:10.1161/CIRCGENETICS.116.001483

Yunpeng Ding, E. Pedersen, G. Svingen, Ø. Helgeland, J. Gregory, K. Løland, K. Meyer, G. Tell, P. Ueland, O. Nygård

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引用次数: 4

Abstract

Background—Serine and glycine interconversion and methylenetetrahydrofolate dehydrogenase 1 (MTHFD1)–mediated 1-carbon transfer are the major sources of methyl groups for 1-carbon metabolism. Recently, plasma glycine and a common polymorphism in MTHFD1 have been associated with risk of acute myocardial infarction (AMI). It is, therefore, of interest to explore if these 2 pathways interact in relation to AMI. Methods and Results—A total of 2571 participants in the WENBIT (Western Norway B Vitamin Intervention Trial) undergoing coronary angiography for stable angina pectoris were studied. Associations of plasma serine and glycine concentrations with risk of AMI across 2 common and functional MTHFD1 polymorphisms (rs2236225 and rs1076991) were explored in Cox regression models. During a median follow-up of 4.7 years, 212 patients (8.2%) experienced an AMI. In age- and sex-adjusted analyses, plasma glycine (P<0.01), but not serine (P=0.52), showed an overall association with AMI. However, interactions of MTHFD1 rs2236225 polymorphism with both plasma serine and glycine were observed (Pinteraction=0.03 for both). Low plasma serine and glycine were associated with an increased risk of AMI among patients carrying the rs2236225 minor A allele. Similarly, low plasma glycine showed stronger risk relationship with AMI in the rs1076991 CC genotype carriers but weaker associations in patients carrying the minor T allele (Pinteraction=0.02). Conclusions—Our results showed that 2 common and functional polymorphisms in the MTHFD1 gene modulate the risk associations of plasma serine and glycine with AMI. These findings emphasize the possible role of the MTHFD1 in regulating serine and glycine metabolism in relation to atherosclerotic complications. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00354081.

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亚甲基四氢叶酸脱氢酶1多态性改变血浆甘氨酸和丝氨酸与稳定型心绞痛患者急性心肌梗死风险的关系

丝氨酸和甘氨酸的相互转化和亚甲基四氢叶酸脱氢酶1 (MTHFD1)介导的1-碳转移是1-碳代谢甲基的主要来源。最近，血浆甘氨酸和MTHFD1的常见多态性与急性心肌梗死(AMI)的风险相关。因此，探索这两种途径是否与AMI相互作用是很有意义的。方法与结果:在WENBIT(西挪威B族维生素干预试验)中，共有2571名接受冠状动脉造影的稳定型心绞痛患者进行了研究。通过Cox回归模型探讨血浆丝氨酸和甘氨酸浓度与2种常见和功能性MTHFD1多态性(rs2236225和rs1076991)的AMI风险之间的关系。在中位4.7年的随访期间，212名患者(8.2%)发生AMI。在调整年龄和性别的分析中，血浆甘氨酸(P<0.01)与AMI总体相关，而丝氨酸(P=0.52)与AMI总体相关。然而，MTHFD1 rs2236225多态性与血浆丝氨酸和甘氨酸均存在相互作用(p - interaction=0.03)。低血浆丝氨酸和甘氨酸与携带rs2236225小A等位基因的患者AMI风险增加相关。同样，在rs1076991 CC基因型携带者中，低血浆甘氨酸与AMI的风险关系更强，而在携带次要T等位基因的患者中，相关性较弱(p互作=0.02)。结论-我们的研究结果表明，MTHFD1基因的2个常见和功能性多态性调节血浆丝氨酸和甘氨酸与AMI的风险关联。这些发现强调了MTHFD1在动脉粥样硬化并发症中调节丝氨酸和甘氨酸代谢的可能作用。临床试验注册-网址:http://www.clinicaltrials.gov。唯一标识符:NCT00354081。

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来源期刊

Circulation-Cardiovascular Genetics CARDIAC & CARDIOVASCULAR SYSTEMS-GENETICS & HEREDITY

CiteScore

3.95

自引率

0.00%

发文量

期刊介绍： Circulation: Genomic and Precision Medicine considers all types of original research articles, including studies conducted in human subjects, laboratory animals, in vitro, and in silico. Articles may include investigations of: clinical genetics as applied to the diagnosis and management of monogenic or oligogenic cardiovascular disorders; the molecular basis of complex cardiovascular disorders, including genome-wide association studies, exome and genome sequencing-based association studies, coding variant association studies, genetic linkage studies, epigenomics, transcriptomics, proteomics, metabolomics, and metagenomics; integration of electronic health record data or patient-generated data with any of the aforementioned approaches, including phenome-wide association studies, or with environmental or lifestyle factors; pharmacogenomics; regulation of gene expression; gene therapy and therapeutic genomic editing; systems biology approaches to the diagnosis and management of cardiovascular disorders; novel methods to perform any of the aforementioned studies; and novel applications of precision medicine. Above all, we seek studies with relevance to human cardiovascular biology and disease. Manuscripts are examined by the editorial staff and usually evaluated by expert reviewers assigned by the editors. Both clinical and basic articles will also be subject to statistical review, when appropriate. Provisional or final acceptance is based on originality, scientific content, and topical balance of the journal. Decisions are communicated by email, generally within six weeks. The editors will not discuss a decision about a manuscript over the phone. All rebuttals must be submitted in writing to the editorial office.