Association between the -174 G/C promoter polymorphism of the interleukin-6 gene and cardiovascular disease risk factors in Brazilian older women

Abstract

In worldwide studies, interleukin-6 (IL-6) is implicated in age-related disturbances. The aim of the present report was to determine the possible association of IL-6 -174 C/G promoter polymorphism with the cytokine profile as well as with the presence of selected cardiovascular risk features. This was a cross-sectional study on Brazilian women aged 60 years or older. A sample of 193 subjects was investigated for impaired glucose regulation, diabetes, hypertension, and dyslipidemia. Genotyping was done by direct sequencing of PCR products. IL-6 and C-reactive protein were quantified by high-sensitivity assays. General linear regression models or the Student t-test were used to compare continuous variables among genotypes, followed by adjustments for confounding variables. The chi-square test was used to compare categorical variables. The genotypes were consistent with Hardy-Weinberg equilibrium proportions. In a recessive model, mean waist-to-hip ratio, serum glycated hemoglobin and serum glucose were markedly lower in C homozygotes (P = 0.001, 0.028, and 0.047, respectively). In a dominant hypothesis, G homozygotes displayed a trend towards higher levels of circulating IL-6 (P = 0.092). Non-parametric analysis revealed that impaired fasting glucose and hypertension were findings approximately 2-fold more frequent among G homozygous subjects (P = 0.042 and 0.043, respectively). Taken together, our results show that the IL-6 -174 G-allele is implicated in a greater cardiovascular risk. To our knowledge, this is the first investigation of IL-6 promoter variants and agerelated disturbances in the Brazilian elderly population.

Inflammatory markers, endothelial function and cardiovascular risk

“…The protective action is triggered by physiological stimuli such as the shear stress exerted by blood flow against endothelial cells, which results in basal production of NO, maintaining the blood vessel in a constant state of vasodilation. 5,10 Nitric oxide plays an active part in many of the protective functions performed by the intact endothelium and, in conjunction with Prostacyclin-2 (PGI-2), it exerts a potent antiatherogenic effect, preventing platelet adhesion and aggregation. 13 Palmer et al conducted an in vivo study that clearly demonstrated how NO and ET-1, which have opposing effects, regulate vascular tone and arterial blood pressure.…”

“…33 Since IL-6 is involved in a series of immunological activities, in particular synthesis of acute phase substances in the liver, it is an important inflammatory marker, because it is involved in metabolic regulation of CRP. 10 Both IL-6 and its receptor (gp130), are widely expressed during an inflammatory reaction, leading to undesirable effects on several organs. 10 Normally IL-6 is expressed in low concentrations, except during infections, traumas or in the presence of other stressing factors.…”

“…10 Both IL-6 and its receptor (gp130), are widely expressed during an inflammatory reaction, leading to undesirable effects on several organs. 10 Normally IL-6 is expressed in low concentrations, except during infections, traumas or in the presence of other stressing factors. Estrogen and testosterone are among the many factors that regulate expression of the IL-6 gene.…”

“…This process results in reduced production of NO. 10 It is the relationship between CRP and eNOS deficiency that appears to be the important point in atherogenesis and this influence can be easily observed by analysis of cultured endothelial cells from the human aorta. After pre-incubation with CRP, expression of eNOS (normally abundant in this type of culture) is significantly reduced, leading to a significant increase in adhesion molecule levels (Figure 2).…”

“…During an inflammatory reaction, IL-6 and CRP can have undesirable effects on a number of organs. 10 Increases in serum IL-6 and CRP levels can cause heart failure and hypercholesterolemia can damage the endothelium, causing endothelial dysfunction, which is very often related to atherosclerosis and cardiovascular events. 7 …”