The association between the minor RFLP alleles and polymorphic gene variants (probably the apo AI, apo CIII, or both genes) which enhance liability to CHD accounted for almost 20% of total CHD in this population.
Within the apolipoprotein A-I-C-III-A-IV gene cluster, the Ssti polymorphism in the 3' untranslated region of the apolipoprotein C-III gene is the variant site most consistently and strongly associated with raised plasma triglyceride levels and coronary artery disease.
Therefore, VLDL particles with apoC-III may play a central role in identifying the high risk of coronary heart disease in hypertriglyceridemia, but their substantial prevalence in normolipidemics may be of clinical significance as well.
Association of the Sst-I polymorphism at the APOC3 gene locus with variations in lipid levels, lipoprotein subclass profiles and coronary heart disease risk: the Framingham offspring study.
Examination of 9 single nucleotide polymorphisms (SNPs) in this group revealed that homozygotes for APOA4 S347 had significantly increased risk of CHD [hazard ratio (HR) of 2.07 (95%CI 1.04 to 4.12)], whereas men homozygous for APOC3 1100T were protected [HR 0.28 (95%CI 0.09 to 0.87)].
The multivariate model included 512 men with coronary artery disease from the REGRESS study who were completely genotyped for eight polymorphisms selected in the univariate procedure (ie, APOA1 G(-75)A, ABCA1 C(-477)T, ABCA1 G1051A, APOC3T3206G, APOE Arg158Cys, LIPC C(-514)T, LPL Asn291Ser and LPL Ser447Stop).
The -1131 T>C and S19W APOA5 gene polymorphisms are associated with high levels of triglycerides and apolipoprotein C-III, but not with coronary artery disease: an angiographic study.
The present study investigated genetic variation in the 3' flanking region of ApoA-I (PstI), the 3' untranslated region of ApoC-III (SstI) and intron 2 of ApoA-IV (XbaI) in 435 type 2 diabetes mellitus patients, divided according to the presence or absence of coronary heart disease (CHD).
Synergistic effects of the apolipoprotein E epsilon3/epsilon2/epsilon4, the cholesteryl ester transfer protein TaqIB, and the apolipoprotein C3 -482 C>T polymorphisms on their association with coronary artery disease.
We identified the haplotype S2/C with a significant increased risk (P < 0.001) to coronary artery disease with increased levels of circulating triglycerides compared to other haplotypes in patients.
ApoC-III levels determined the development of diabetes [RR 1.56 (95%CI 1.21; 2.01)] and CHD [RR 1.38 (1.10; 1.72) for an increment of 14%], after adjustment for confounders.
Lower concentrations of apoC-III and LDL with apoC-III are associated with reduced risk of coronary heart disease (CHD) in epidemiologic studies independent of traditional risk factors.
PubMed, EMBASE and Cochrane library databases (up to March 2013) were systematically searched to identify studies evaluating the association between ApoC3 polymorphisms and CHD risk.
Two new studies report that triglyceride (TG)-lowering mutations in APOC3 reduce coronary heart disease (CHD) (Crosby et al., 2014; Jørgensen et al., 2014).
In humans, loss-of-function mutations in APOC3 are associated with reduced plasma TG levels and reduced risk for ischemic vascular disease and coronary heart disease.
Furthermore, identification of rare loss-of-function variants in genes such as PCSK9, NPC1L1, APOC3 and APOA5, which cause a markedly decreased risk of CHD and no adverse side effects, illustrates the power of translating genetic findings into novel mechanistic information and provides some optimism for the future of developing novel drugs, given the many genes associated with CHD in GWASs.