Study of IL-6 gene promoter polymorphism in patients with primary iron overload

Abstract

Primary iron overload (IO) has been linked to a pro-inflammatory state and to increased risk of cardiovascular disease (CVD). Among the markers of inflammation associated with CVD, high sensitive C-reactive protein (hsCRP) and interleukin 6 (IL-6) are the most relevant. The gene promoter of IL-6 has a single nucleotide polymorphism (SNP) on position -174 (G/C), which regulates its transcription. The aim of this study was to o evaluate the SNP -174 G/C and its interaction with risk factors and biomarkers of CVD in patients with primary IO and controls. Thirty-seven men diagnosed with primary IO were studied and compared with sex and age-matched controls. HsCRP concentration was evaluated by automated high sensitive immunoturbidimetric assay and IL-6 by enzyme immunoassay. SNP -174
G/C was evaluated by PCR-RFLP. HsCRP was higher and IL-6 lower in patients compared to controls. The genotyping of the SNP -174 G/C showed significantly different genotype frequencies between patients (43% CC, 43% CG and 14% GG) and controls (10% CC, 41% CG and 49% GG) (OR = 4.09, 95% CI = 2.06 to 8.13, p < 0.0001), being in Hardy-Weinberg equilibrium. The multiple logistic regression analysis showed that IO was independently and significantly associated, firstly, with the CC homozygosis (OR: 7.05, p < 0.01; IC 95%: 1.66 – 29.86) and then with serum iron. It was concluded that patients patients with primary IO presented higher frequency of the C allele in IL-6 gene promoter, thereby conditioning the presence of lower circulating IL-6.