The RANTES -403G > A promoter polymorphism in Korean men: Association with serum RANTES concentration and coronary artery disease

Abstract

In the present study we investigated the association of the RANTES (regulated upon activation, normal T-cell expressed and secreted) -28C>G and -403G>A promoter polymorphisms with the concentration of serum RANTES and CAD (coronary artery disease) in Korean men. We included 553 male CAD patients with (n=176) or without (n=377) Type 2 diabetes, aged 40-65 years with previous myocardial infarction ( approximately 50%) or angiographically confirmed CAD ( approximately 50%), and 416 aged-matched healthy male controls. The main outcome measures were the OR (odds ratio) of CAD risk and the serum RANTES concentration evaluated by sandwich ELISA. Although the RANTES -28C>G genotype had no significant association with CAD risk, the presence of the minor allele of the RANTES -403G>A single nucleotide polymorphism was associated with a lower risk of CAD {OR 0.70 [95% CI (confidence interval) 0.54-0.92], P=0.011} after adjusting for age, BMI (body mass index), cigarette smoking and alcohol consumption. Serum RANTES concentrations were significantly associated with the -403G>A genotype in controls (G/G: 44.7+/-3.3 ng/ml, G/A: 36.5+/-2.0 ng/ml, A/A: 28.7+/-2.5 ng/ml; P<0.001), non-diabetic CAD patients (G/G: 50.9+/-3.0 ng/ml, G/A: 42.2+/-2.6 ng/ml, A/A: 41.3+/-4.4 ng/ml; P<0.05) and diabetic CAD patients (G/G: 58.5+/-3.5 ng/ml, G/A: 49.6+/-4.1 ng/ml, A/A: 42.2+/-4.3 ng/ml; P<0.05); however, such associations were not observed in the subgroup of CAD patients taking lipid-lowering medication. Moreover, serum RANTES was positively correlated with C-reactive protein (r=0.289, P<0.001) and platelet counts (r=0.253, P<0.001). The results of the present study demonstrate that the RANTES -403A allele is associated with lower serum RANTES concentrations and consequently with reduced CAD risk.