Advanced glycation end-product receptor gene (RAGE) polymorphisms modulate acute coronary syndrome risk 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 substitution polymorphisms (SNPs), rs2070600 G/A and rs184003 G/T, in the gene encoding the receptor for advanced glycation end products ( RAGE ) may determine predisposition to 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 chi ² test on a 2x2 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 via Student’s t test or the Mann‒Whitney U test when appropriate. Results For the rs184003 G/T polymorphism, the frequency of genotypes containing the polymorphic 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) and was associated with lower high density lipoprotein (HDL) cholesterol levels (mean 1.02 mmol/l vs 1.14 mmol/l, p = 0.01) and higher mean troponin I concentrations at the time of ACS (32.3 ng/ml vs 24.4 ng/ml, p = 0.03). 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). Conclusions Our findings suggest a possible role of the rs184003 SNP in the gene encoding RAGE in shaping the genetic predisposition to CAD and ACS in the Polish population. However, they do not confirm the association of the studied SNPs with the occurrence of ACS at a young age.