Role of osteoprotegerin rs3102735 gene polymorphism in acute ischemic stroke patients

Abstract

Abstract Background Ischemic stroke ranks third among leading causes of death and disability. Both endothelial and vascular smooth muscle cells generate osteoprotegerin (OPG). Ischemic stroke and its severity may be enhanced by the OPG rs3102735 gene polymorphism. Our research aims to investigate OPG rs3102735 gene polymorphism role in ischemic stroke risk and to assess its association with stroke severity at presentation and degree of vascular stenosis and evaluate its potential as a predictor of stroke severity. Fifty people with acute ischemic stroke as well as fifty controls were studied. The NIHSS and ASPECTS were utilized to evaluate stroke severity and the infarction size, respectively. All subjects underwent extracranial carotid duplex study and molecular assessment for genotyping of OPG rs3102735) gene polymorphism. Results Stroke patients had markedly higher concentrations of OPG in the plasma than controls (311.60 ± 109.48 versus 240.20 ± 75.96 mmol/ml, p = 0.001). The optimal plasma OPG cutoff value for the predicting the occurrence of stroke was determined to be > 250 mmol/ml, the 95% confidence interval (CI) was (0.625–0.843), sensitivity was 68% and specificity was 72%. Ischemic stroke had a significantly different genotype distribution for the OPG rs3102735 gene polymorphism than did controls (36 CC, 13 CT, and 1 TT) versus (28 CC, 15 CT, and 7 TT) respectively. Stroke patients had a significantly greater CC + CT genotype than controls did (P = 0.041), also they had a higher propensity for carrying the C allele than the T allele (P = 0.017). Carotid intima medium thickness and the NIHSS both had positive correlations with OPG serum level (r = 0.39, p = 0.02 and r = 0.4, p = 0.02, respectively), whereas ASPECTS had an inversed correlation (r = − 0.65, p = 0.001). Conclusions The current study shows that as an independent risk factor, increased plasma OPG level, may participate in the atherothrombotic ischemic stroke pathophysiology, in addition, genetic variants in the OPG gene (rs3102735) are a separate risk factor for large artery atherosclerosis and plasma OPG level can serve as a biomarker to determine the severity of a stroke.

Keywords

• Ischemic stroke
• Osteoprotegerin
• OPG rs3102735 gene polymorphism