P574The association between inflammatory mediator gene markers and cardiovascular disease

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Chronic persistent low-grade inflammation is considered a key mechanism contributing to the development of age-related cardiovascular disease. It is hypothesized that the changes happening in cardiovascular system during the process of aging are caused by the imbalance between pro- and anti-inflammatory systems. The aim of the current study was to investigate an association between inflammatory mediator gene markers and cardiovascular phenotypes (essential ypertension, myocardial infarction, sudden cardiac death).

Study group consisted of 2229 individuals (550 patients with essential hypertension, 649 patients with myocardial infarction, 855 healthy individuals without any history of cardiovascular disease, and 175 cases of sudden cardiac death confirmed by autopsy. Genotyping was performed using standard PCR-RFLP procedure. Data were analyzed using IBM SPSS v.21 and PLINK software.

We detected an association between essential hypertension and IL10 rs1800872 (-627C>A) and IL1B rs16944 (-511C>T) polymorphisms. Increased risk of the disease development was observed in IL10 rs1800872*A allele (OR=1.48, P=0.04) and IL1B rs16944 *T/C genotype carriers (OR=1.64, P=0.03). Myocardial infarction was found to be associated with ICAM1 rs5498 (K469E), CCL2 rs1024611 (-2518A>G), SELE rs2076059 (3832C>T) polymorphic loci. Increased risk of myocardial infarction was associated with the carrier status of CCL2 rs1024611*G/G genotype (OR=2.75, P<0.001) and SELE rs2076059*T/T genotype (OR=1.64, P=0.03), while ICAM1*K/K genotype carriers had decreased risk of myocardial infarction (OR=0.6, P=0.01). Sudden cardiac death was associated with IL6 rs1800796 (-572G>C) and TNF rs1800629 (-308G>A) genetic markers. Increased risk of sudden cardiac death was associated with IL6 rs1800796*C allele (OR=2.16, P=0.01) and TNF rs1800629*G/G genotype (OR=4.25, P=0.04), while IL6*G/G genotype and IL6*G allele were associated with lower risk of sudden cardiac death (OR=0.38, P=0.015 and OR=0.46, P=0.01, respectively).

Our findings provide an evidence for association between cardiovascular traits and polymorphic markers located in the genes encoding for inflammatory mediators (interleukins, chemokines, selectines and adhesion molecules). Further investigation is needed to establish the functional role of these polymorphisms in the development of cardiovascular disease.

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