Association of variants of the <i>APOE</i>, <i>CETP</i> genes and the 9P21.3 chromosomal region with coronary heart disease, myocardial infarction and acute heart failure

Abstract

   A relevant task for the healthcare system is to identify the groups most predisposed to cardiovascular diseases (CVD) of atherosclerotic genesis. Risk stratification is an important component of choosing a management strategy for both CVD patients and those with risk factors. The individual risk of an unfavorable cardiovascular outcome is determined by genetic factors in addition to lifestyle factors.   The aim of the work was to examine the association of variants of the APOE, CETP and chromosomal region 9p21.3 with coronary heart disease (CHD), myocardial infarction (MI) and acute heart failure (ACF) in a sample of residents of Novosibirsk.   Material and methods. Sample: 2516 participants of the HAPIEE project (57.5 ± 0.2 years old, male to female ratio 45:55). The choice of the variants of the APOE, CETP and the chromosomal region 9p21.3 was due to their significant association with CVD according to several studies and meta-analyses. Genotyping of rs708272, rs429358 and rs7412 was performed by Real-Time PCR using TaqMan reagents; genotyping of rs1333049 was performed using a commercial KASP kit.   Results. Allele C of rs1333049 was associated with an increased risk of CHD, MI and AHF in the subgroup of men (p = 0,008) and in the general group (p = 0,002). In the general group, the incidence of CHD, MI and AHF was significantly lower in carriers of the G allele (odds ratio 0.748, 95 % confidence interval 0.606–0.924, p = 0.007). We confirmed the association of the ɛ2/ɛ4 genotype of the APOE gene with CHD, MI and AHF among males (p = 0.007) and in the whole study sample (p = 0.009). In the women subgroup the genotype ɛ2/ɛ2 (p < 0.0001) was associated with CHD, MI and AHF, while in carriers of the genotype ɛ3/ɛ3, the incidence of CHD, MI and AHF was significantly lower (odds ratio 0.675, 95 % confidence interval 0.509–0.894, p = 0,006).   Conclusions. This work shows the association of rs1333049 of chromosomal region 9p21.3 and rs429358&rs7412 of the APOE gene with the risk of CHD, MI and AHF in a sample of residents of Novosibirsk. These variants may be recommended for inclusion into a genetic risk score.