Coronary heart disease (CHD), also known as coronary atherosclerotic heart disease is a kind of thrombotic arterial disease, caused by hypoxia and myocardial ischemia owing to coronary atherosclerotic mediated vascular obstruction as well as coronary functional change [1, 2]. CHD has become one of leading diseases threatening human health and causing mortality, with an estimated 7.2 million individual worldwide die of this disease annually based on the World Health Organization [3]. In 2015, CHD alone caused approximately one of every seven deaths in the United States, and each year, there has emerged about 635,000 Americans who have a new coronary attack [4]. CHD is a complex multifactorial disorder and both non-genetic and genetic factors can contribute to the development and progression of this disease [5]. The non-genetic factors attributed to CHD has been clearly established, including type 2 diabetes, obesity, dyslipidemia, hypertension, low-density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and lifestyle, such as smoking, lack of exercise and high fat diet [6, 7]. Interestingly, there is an inverse relationship between triglyceride (TG) levels and HDL-C levels, and in metabolic syndrome, high LDL levels reduce the TG content of HDL, thus reducing the size of the HDL particle and making it more prone for renal clearance; besides, excess of TG in the HDL particle contribute to HDL dysfunction [8]. Circulating triglyceride-rich lipoproteins from hypertriglyceridemic subjects mediated endothelial inflammation and drive monocyte infiltration into the wall of arterial [9]. Although prime interest was devoted to LDL-C as proatherogenic, TG are considered in the last years to be also proatherogenic and some studies provide evidence for causal involvement of TG-mediated pathways in CHD and the concentration of it (both fasting and non-fasting) in prediction of future cardiovascular disease events [9–14].

Apolipoprotein A5 (APOA5) is a fourthly discovered member of the APOA4/APOC3/APOA1 apolipoprotein cluster and the human APOA5 gene is located at chromosome 11q23 [15]. APOA5 gene comprises four exons and encodes APOA5, a protein of 366 amino acids, which is an effective stimulator of lipoprotein lipase and can facilitate lipoprotein remnant clearance in a LDL receptor-dependent manner [16, 17]. It was reported that nucleotide sequence variations in the APOA5 gene have been correlated to high TG levels, exerting pleiotropic influences on different groups [18]. Apolipoprotein C3 (APOC3) is a significant component of TG-rich lipoproteins and a minor component of HDL [19]. APOC3 gene, also located in the chromosome 11q23, participates in transport and clearance of very-low-density lipoprotein (VLDL), chylomicron remnants, and HDL from the bloodstream [20]. APOC3 encodes a 79-amino-acid glycoprotein, which was produced largely in the liver interfering with receptor induced lipoprotein uptake and inhibiting the activation of lipoprotein lipase [21]. An increasing number of evidence suggested that APOA5 -1131 T > C and APOC3 -455 T > C single nucleotide polymorphisms (SNPs) contribute a substantial role in development of CHD owing to their correlation with increased plasma TGs, which has become the focus of oversea and domestic researchers [22, 23]. Nevertheless, there also emerged contradictory results on the role of APOA5 and APOC3 variants in CHD [24, 25]. In consideration of the controversial results from previous studies, we performed a case–control study to clearly address the correlation of CHD with APOA5 -1131 T > C and APOC3 -455 T > C, which was further confirmed by a following meta-analysis.

The presented study evaluated the correlations of CHD with APOA5 -1131 T > C and APOC3 -455 T > C SNPs. Furthermore, in order to obtain a more conclusive and definitive estimation of the correlation of CHD with the two SNPs, our new case–control study combined with a meta-analysis pooled results from previously published studies were systematically carried out. The overall results of our study suggested that there was a strong link between the two SNPs, APOA5 -1131 T > C and APOC3 -455 T > C, with increased risk of CHD.

CHD, also known as coronary artery disease, is a multifactorial disorder, the risk of which was involved with some plasma lipids such as TC as well as TG, LDL-C, and HDL cholesterol (HDL-C), and lifestyles including smoking, alcohol consumption [39]. Additionally, both hypertension and diabetes mellitus were also involved in the development and progression of CHD [40]. In our study, we compared the clinical data and biochemical indexes of subjects between CHD patients and health individual, and the results demonstrated that CHD patients had longer history of smoking, drinking, hypertension along with diabetes mellitus, and lower levels of TC, HDL-C and LDL-C compared to health individuals.

One of our results in our study was that APOA5 -1131 T > C SNP is likely to increase the risk of CHD, which was further demonstrated by the following meta-analysis. APOA5, encoding apolipoprotein AV, is expressed in the liver and circulates on very low density lipoproteins, chylomicrons CM and HDL [41]. Apolipoprotein AV participates in the catabolism of triglyceride-rich particles by exerting the activation of lipoprotein lipase, leading to the promotion of TG hydrolysis [29]. The rare haplotype in vivo would result in the reduction of apolipoprotein AV synthesis, and thus there was less apolipoprotein AV that was available for incorporation into triglyceride-rich particles, with the consequence of less circulating apolipoprotein AV to promote the activation of lipoprotein lipase or to affect its receptor-mediated clearance, eventually developing atherosclerosis [10, 42]. In our study, CC and TC + CC frequencies of APOA5 -1131 T > C were higher compared to health individuals. Consist with our results, Sarwar et al. reported that the -1131 T > C (rs662799) promoter polymorphism of the APOA5 gene was related to higher VLDL concentration as well as smaller HDL particle size pathways by which triglyceride could exert influence on the risk of CHD [10].

Another results in the current study suggested that APOC3 -455 T > C had potential to increase the risk of CHD, which also further demonstrated by our meta-analysis. The metabolism of circulating particles rich in TGs is closely influenced by their content in APOC3 encoded by APOC3 gene, and it is a component that interferes with the lipoprotein lipase-triggered hydrolysis of these particles [21]. The APOC3 gene is transcriptionally down-regulated through insulin levels, and sequences in the promoter region with high adherence for the nuclear transcription factors inducing the insulin response are highly polymorphic [43]. Variants at positions −455 in APOC3 gene have been shown to have a decreased affinity for the nuclear transcription factors inducing the response, which is also relevant to a half of insulin-generated downregulation of APOC3 gene expression [44]. APOC3 is an important inhibitor of the lipolysis of triglyceride-rich lipoproteins via countering APOC2 activation of lipoprotein lipase [45]. Interestingly, Hypertriglyceridemia has been accepted by the National Cholesterol Education Program Adult Treatment Panel III as a potent risk factor for the development and progression of CHD [46].

In conclusion, our study demonstrated that APOA5 -1131 T > C and APOC3 -455 T > C SNPs may play potent roles in the development and progression of CHD. On a more practical ground, further researches with larger sample size are needed to examine whether incorporation of the APOA5 -1131 T > C and APOC3 -455 T > C SNPs into a general algorithm including genetic and metabolic variables will help further improving the identification of individuals at early risk of CHD.