IL6 -174 G/C and Fibrinogen-β-455 G/A Polymorphisms in Ischemic Cerebrovascular Disease (ICD).

Ischemic cerebrovascular disease (ICD) is a multi-factorial entity whose anatomopathologic substrate is atherosclerosis. The inflammatory cells migrate to vascular endothelium and release chemokines such as interleukin 6 (IL6), resulting in the atheroma plaque development. The IL6 production induces acute phase proteins synthesis such as fibrinogen.

Objective. The purpose of this case-control study is to analyze the ICD risk associated to the polymorphisms IL6-174 G/C and beta chain of fibrinogen-455 G/A (fibri-β-455). The association of these polymorphisms, classic vascular risks factors and ICD subtypes according to TOAST classification has also been explored.

Methods and patients. A total of 159 ICD diagnosed patients (82 female and 77 male; mean age 67.7±15) were analysed. They were matched for age (±5 years) and sex with a control group (65.6±14) without thrombotic history. AHT, DM, dyslipidaemia and smoking habit data were collected for each group. Polymorphisms were analysed by PCR-RFLP. Serum IL6 was measured by ELISA and fibrinogen by Clauss method. Statistic analysis was made with the SAS v9 software.

Results. Genotype analysis showed a significant higher prevalence of the genotypes G/G and G/C IL6 -174 in the patients (OR: 1.49, IC 95%: 0.95–2.34, p: 0.049). By contrast, the fibri-β-455 genotypes were not different in patients and controls (p= 0.230). When the stroke subtypes were analysed, we found that IL6-174 G/C genotype was more frequent in cardioembolic (60.0%) and atherothrombotic ICD subtypes (58.3%). In relation to fibri-β-455 G/A, the A allele showed a increased prevalence in atherothrombotic stroke (43.2%) (p= 0.049).

We observed an association between the dyslipidaemia and IL6-174 G/C polymorphism (p= 0.034) and smoking habit with fibri-β-455G/A (p= 0.072). No synergic relation were found between IL6-174 G/C and fibri-β-455 G/A. The G allele IL6-174 G/C carriers group presented higher serum IL6 levels than C allele carriers, 5.85 pg/ml (2.9–34.5) vs. 4.94pg/ml (2.5–11.4). Also, allele A fibri-β-455 G/A was associated with a higher fibrinogen levels than G allele, 329 mg/dl (210–686) versus 280 mg/dl (107–783).

Conclusion. There is an association between-174 IL6 G/C polymorphism and ischemic stroke. By contrast, we did not find any association between fibri-β-455 G/A, and ICD. Besides, the analysis performed by ICD subtypes showed an association of this polymorphism and atherothrombotic subtype. These results suggest a relation between smoking habit and fibri-β-455 G/A, and dislypidaemia and-174 IL6 G/C polymorphism.