Interleukin-6 gene -174 G/C promoter polymorphism predicts severity and outcome in acute ischemic stroke patients from north India

Abstract

Background: A guanine/cytosine (G/C) substitution occurring in position -174 of the interleukin-6 (IL-6) gene promoter changes the expression of IL-6 circulating proteins. We evaluated the occurrence of IL-6 -174 G/C polymorphism in patients with acute ischemic stroke and studied its association with stroke severity, outcome, and mortality.

Methods: One hundred patients with acute ischemic stroke and 120 age and sex-matched healthy controls were studied. Genotyping was performed using polymerase chain reaction and restriction enzyme analysis. Serum levels of IL-6 were measured using enzyme-linked immunosorbent assay. Stroke was classified using Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Severity was assessed by the National Institutes of Health Stroke Scale. Outcome measures included modified Rankin Scale (mRS) and Barthel Index (BI) scores at 7 days and 3 and 6 months. Mortality/survival was assessed using the Kaplan-Meier analysis.

Results: The frequency of GG, GC, and CC genotypes did not differ significantly between cases and controls. No association was seen between TOAST subtype and genotype. At the time of admission, stroke was more severe in patients with the GC genotype (P = .03) and less severe in the GG genotype (P = .04). The GC genotype was also associated with higher serum IL-6 levels and poor short-term (BI P = .001; mRS P = .003) and long-term outcomes (BI P = 9 × 10(-5); mRS P = 9 × 10(-5)), while the GG genotype had significantly lower serum IL-6 levels and better short and long-term outcomes (BI P = 3 × 10(-5); mRS P = 2 × 10(-4)). There was significantly lesser mortality in the GG genotype and more in the GC genotype based on the Kaplan-Meier analysis.

Conclusions: Patients with the GC genotype had more severe strokes with poorer short and long-term outcomes and increased mortality. The GG genotype was associated with less severe strokes, better short and long-term prognosis, and survival. The GG genotype appears to be protective against stroke severity, outcome, and mortality.