Angiotensinogen Gene Polymorphism as a Risk of Stroke in Egyptian Patients with Sickle Cell Disease

Abstract

Strokes in sickle cell disease (SCD) children are considered a major cause of morbidity and mortality; SCD patients have a high prevalence and incidence of strokes. This high incidence necessitates identification of high risk patients in an attempt for early management to prevent cerebrovascular events. This study was aimed to investigate the potential associations between angiotensinogen M235T polymorphism and susceptibility to stroke in Egyptian patients with SCA. Fifty patients with SCD confirmed by HPLC are included in this study and fifty healthy controls. We collected all details about disease history and possible risk factors for stroke. All recruited subjects were subjected to through clinical assessment. Blood samples were collected from SCD patients and controls subjected to DNA extraction from peripheral blood, genotyping by PCR and restriction enzyme digest (RFLP), single nucleotide polymorphisms (SNPs) for AGT polymorphism. Our results showed a significant higher incidence of the mutant (T) allele in patients group than control (X2= 4.040, P = 0.044). There was a highly significant difference between those with and without stroke as regard the genotype (X2 = 17.268, P-value =<0.001) and alleles (X2 =13.177, P-value = <0.001).There was a higher incidence of (TT) mutant genotype in patients with stroke. In addition, there was a higher incidence of (T) mutant allele in patients with stroke. Five of six patients with stroke had TT and one had MT. There was statistically significant higher rate of consanguineous marriage in those with stroke than those without (X2 = 3.835, P= 0.040). There was significant difference between those with and without stroke as regard duration on regular transfusion (X2 = 2.477, P-value = 0.019) or blood exchange (X2 = 50.000, P-value = < 0.001). All patients with stroke were put on regular blood exchange and hydroxyurea after development of stroke. There was highly significant association between genotype and alleles with both hemoglobin A1 (k=13.297, p value =< 0.001), (Z=-2.511, p value= 0.012) respectively and with hemoglobin S (k=16.767, p value =< 0.001), (Z=-2.705, p value= 0.557) respectively. Multivariate logistic regression analysis showed that duration on hydroxyurea, duration on regular transfusion, genotype and alleles are significant predictors for development of stroke.