The impact of homocysteine on the risk of coronary artery diseases in individuals with diabetes: a Mendelian randomization study

Abstract

Aims Observational studies have reported that homocysteine (Hcy) is associated with an increased risk of coronary artery disease (CAD) in individuals with diabetes, though controversy remains. The present study aimed to investigate the causal association between Hcy and CAD in individuals with diabetes. Methods A 2-sample Mendelian randomization (MR) study was designed to infer causality. Genetic summary data on the association of single nucleotide polymorphisms (SNPs) with Hcy were extracted from the hitherto largest genome-wide association study (GWAS) of up to 44,147 individuals of European ancestry. SNP-CAD data were obtained from another recently published GWAS which included 15,666 individuals with diabetes (3,968 CAD cases, 11,696 controls). The fixed-effects inverse variance-weighted method was employed to calculate the effect estimates. Other robust methods and leave-one-out analyses were used in the follow-up sensitivity analyses. Potential pleiotropy was assessed with the MR-Egger intercept test. Results The 2-sample MR analysis suggested no evidence of an association between genetically predicted plasma Hcy levels and CAD risk in individuals with diabetes (odds ratio = 1.14, 95% confidence interval: 0.82–1.58, p = 0.43) using 9 SNPs as instrumental variables. Similar results were observed in the follow-up sensitivity analyses. The MR-Egger intercept test indicated no evidence of directional pleiotropy (intercept = 0.03, 95% confidence interval: − 0.08–0.03, p = 0.35). Conclusion This 2-sample MR analysis found no evidence of a causal association between plasma Hcy levels and CAD risk in individuals with diabetes.

Distribution Pattern of Atherosclerosis in the Abdomen and Lower Extremities and Its Association with Clinical and Hematological Factors

“…In a meta-analysis study with diabetic patients, there was no causal association between plasma homocysteine levels and coronary artery disease. 21 However, it has been reported that homocysteine causes oxidative stress, endothelial dysfunction, vascular remodeling, and atherosclerosis by inducing the phenotypic switch of VSMCs from a contractile to a synthetic phenotype. 7 , 22 , 23 Although the relevance between homocysteine and the development of atherosclerosis is not clear, the present study suggests that the high level of homocysteine in the blood may be associated with atherosclerosis in the infrainguinal muscular arteries.…”

The relationship between hyperhomocysteinemia and total coronary artery occlusion: a cross-sectional study from Southwest China

“…Smoking promoted dyslipidemia, and hyperhomocysteinemia contributed to homocysteine-associated LDL-C atherosclerosis [46]. Of note, hyperhomocysteinemia was found to not be a risk factor for coronary atherosclerotic heart disease in diabetic people [48] something that was expanded upon and confirmed via MRI analysis of several diabetic individuals [49].…”

Predictive nomogram for coronary heart disease in patients with type 2 diabetes mellitus

“…High levels of HCY can increase the risk of thrombosis, oxidative stress, and endothelial dysfunction. Some studies have found elevated HCY levels to be a risk factor for CHD (30).…”