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 age-related disturbances in the Brazilian elderly population.
Highlights
Inflammation is recognized as a central component of cardiovascular disease (CVD), even though the underlying regulation and molecular mechanisms remain unclear [1]
Because a large fraction of cardiovascular events occurs in people aged 60 years or older and the IL-6 promoter polymorphism has not been studied extensively among aged women, we examined the effects of the -174 C/G genotypes on CVD risk factors in a subset of subjects from the Elderly Health Promotion Project held in Brasília, Brazil
In a co-dominant model, no significant differences in age, Body mass index (BMI), fasting glucose levels, HbA1c levels, serum lipids, liver marker concentration, leukocyte count, or C-reactive protein (CRP) were observed between subjects carrying the three genotypes
Summary
Inflammation is recognized as a central component of cardiovascular disease (CVD), even though the underlying regulation and molecular mechanisms remain unclear [1]. It has been reported that the common -174 C/G polymorphism in the promoter region of human IL-6 regulates its transcription in vitro, with the G www.bjournal.com.br allele showing increased transcriptional activity both under basal conditions and in response to inflammatory stimuli such as lipopolysaccharides or IL-1 [3,4,5]. In addition to the issue of genotype-related expression levels, it is recognized that an age-related increase in serum IL-6 levels takes place among men and women [10], beginning as early as at 30-40 years of age [11], being prevalent even in people devoid of any overt acute or chronic disease [12], becoming prominent in later life [13,14], and acting as a predictor of mortality independent of pre-existing morbidity [15]
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