Abstract
BackgroundAdaptor-related protein complex 2 alpha 2 subunit (AP2A2) gene encodes a protein-a subunit of the AP-2 adaptor protein complex. Evidence has revealed that benzodiazepine receptor-associated protein 1 (BZRAP1) is abundant in the hippocampus with potential effects on brain diseases. Recently, an epidemiological study reported that two variants (rs7396366 and rs2526378) closest to the AP2A2 and BZRAP1 genes are associated with higher plasma lipids and Alzheimer’s disease. Whether the two single nucleotide polymorphisms (SNPs) are actually relevant to coronary artery disease (CAD) and CAD severity remains elusive. Our aim was to assess whether these two SNPs are relevant to CAD and its severity in a Chinese population.MethodsThree hundred and thirty-five patients with documented CAD (282 stable CAD, 28 non-ST-segment elevation myocardial infarction, 25 ST-segment elevation myocardial infarction), and 372 non-CAD controls were included in the study. The participants were divided into two groups according to coronary angiography results. CAD patients were further demarcated into subgroups with one-, two-, or three-vessel stenosis. Genotypes at rs7396366 and rs2526378 were examined using polymerase chain reaction-ligase detection reaction. The association between these two SNPs with CAD and its severity were analyzed.ResultsThe frequency of the rs7396366 TT genotype was significantly higher in CAD patients than in controls (13.7% vs. 7.8%, 95% CI: 1.15–3.07, P = 0.014). Subjects with a variant genotype T allele had an increased risk of CAD compared with G allele carriers (additive model: 95% CI: 1.21–3.35, P = 0.008). After adjustment for traditional cardiovascular risk factors, analysis of the dominant models involving rs7396366 also showed that T allele carriers had a significantly higher risk for CAD than G allele carriers had (dominant model: OR 1.48, 95% CI: 1.03–2.14, P = 0.035). Age, sex, type 2 diabetes mellitus, fasting plasma glucose, and the TT genotype in rs7396366 were significantly associated with three-vessel lesions. Despite these significant outcomes of rs7396366, information on rs2526378 showed no significant difference between CAD patients and non-CAD controls.ConclusionOur results show that the T allele and TT genotype in rs7396366, closest to the AP2A2 gene, are linked to an increased risk of CAD and its severity in a Chinese population.
Highlights
Adaptor-related protein complex 2 alpha 2 subunit (AP2A2) gene encodes a protein-a subunit of the AP-2 adaptor protein complex
To advance our knowledge of the functions of AP2A2 and benzodiazepine receptor-associated protein 1 (BZRAP1) in coronary artery disease (CAD) and to seek new methods predicting CAD earlier, we studied the association between the two single nucleotide polymorphisms (SNPs) and the risk of CAD and its severity based on a Chinese population
Both stable CAD (SCAD) and non-ST-segment elevation myocardial infarction (NSTEMI) subgroups showed significant differences in age, sex, Type 2 diabetes mellitus (T2DM), and fasting plasma glucose (FPG) levels compared with controls
Summary
Adaptor-related protein complex 2 alpha 2 subunit (AP2A2) gene encodes a protein-a subunit of the AP-2 adaptor protein complex. An epidemiological study reported that two variants (rs7396366 and rs2526378) closest to the AP2A2 and BZRAP1 genes are associated with higher plasma lipids and Alzheimer’s disease. Coronary artery disease (CAD), the most common CVD, remains the major cause of morbidity and mortality in the largest developing country, China [3, 4]. Adaptor-related protein complex 2 (AP2) is a protein complex that is involved in the formation of clathrin-coated pits and functions as an adaptor by linking lipid and protein membrane components with the clathrin lattice [11]. It has four non-identical polypeptide chains [12]. AP2 has evolved as a key regulatory node to coordinate clathrin-coated pits formation and ensure high spatial and temporal regulation of clathrin-mediated endocytosis [14]
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