Advanced glycation end-product receptor gene (RAGE) polymorphisms in patients with acute coronary syndrome - a case-control study in the Polish population.

BACKGROUND

The development of coronary artery disease (CAD) is the result of complex interactions between environmental and genetic factors. While the former is well known, the genetic factors that predispose individuals to the development of CAD are still under investigation. The aim of our study was to investigate whether single nucleotide polymorphisms (SNPs) in the gene encoding the receptor for advanced glycation end products (RAGE), specifically rs2070600 G/A and rs184003 G/T, may determine predisposition to acute coronary syndrome (ACS) and severity of coronary artery disease (CAD) in the Polish population.

METHODS

Two RAGE SNPs were genotyped in 336 patients with a history of acute coronary syndrome (ACS): 175 < 50 years, 161 ≥ 50 years, and 160 ethnically, age- and sex-matched controls via the restriction fragment length polymorphism method. Allele frequencies were compared between groups via the chi2 test on a 2 × 2 contingency table. Genotype distribution was analyzed assuming three modes of inheritance: dominant, codominant, or recessive. The values of the variables between the study groups were compared using Student's t-test or the Mann-Whitney U test, as appropriate.

RESULTS

For the rs184003 G/T polymorphism, the frequency of genotypes containing the T allele (GT + TT) was significantly greater in patients with a history of ACS than in healthy age- and sex-matched controls (28.87% vs. 11.25%, p < 0.0001, OR = 3.2 [95% CI: 1.86-5.52]). Moreover, individuals possessing this allele had lower high-density lipoprotein (HDL) cholesterol levels (mean 1.02 mmol/l vs. 1.14 mmol/l, p = 0.01) and higher median troponin I concentrations at the time of ACS (32.2 ng/ml vs. 24.4 ng/ml, p = 0.04). These genotypes were also significantly less common in patients with ACS before the age of 50 than in those diagnosed later (20.0% vs. 38.5%, p = 0.0002, OR = 0.4 [95%CI: 0.25-0.65]). In the case of rs2070600 G/A polymorphism, the genotype and allele frequencies were not significantly different between the study groups and subgroups.

CONCLUSIONS

Our findings suggest that the rs184003 SNP in the RAGE gene may play a role in determining genetic susceptibility to CAD and ACS in the Polish population. However, they do not support the hypothesis that the studied SNPs impact the incidence of ACS at a young age.