ABSTRACT
Background: Sickle cell disease (SCD) is a hereditary disorder characterized by hemolytic anemia with different clinical manifestations. Patients with SCD exhibit a chronic inflammatory state and reduced length and quality of life. Interleukin-1 ß (IL-1ß) is important in acute and chronic diseases; and its single nucleotide polymorphisms (SNP) have been considered as predictors of prognosis in several inflammatory conditions. This study aimed at exploring IL-1ß (+3954C/T) SNP as a potential genetic modifier and/or predictor of SCD clinical and laboratory phenotypes. Materials and Methods: This cross-sectional study involved 50 SCD patients and 50 age, sex and ethnicity-matched healthy individuals. IL-1ß (+3954C/T) SNP was identified by PCR-RFLP. Associations between IL-1ß (+3954 C/T) SNP and the clinical and laboratory profiles of patients with SCD were studied. Results: It was found that the homozygous mutant genotype TT was significantly higher in cases compared to controls [13(26%) vs. 3(6%) respectively; p=0.006, OR (95%CI): 5.505(1.460-20.756)]. The homozygous mutant genotype TT was associated with a higher mean pulmonary arterial pressure when compared to the CC and CT genotype (42.62 vs. 33.49 mmHg, p<0.001). Conclusion: There is an increased prevalence of the mutant genotype of IL-1ß +3954 SNP in Egyptian SCD patients. Regarding disease complications, the mutant genotype was more prevalent in cases complicated by pulmonary hypertension. These findings point to the possible role of IL-1ß +3954 SNP in the pathophysiology of SCD and its manifestations.
ABSTRACT
BACKGROUND: Glutathione S-transferases (GSTs) are a polymorphic superfamily of multifunctional enzymes known to play an important role in the detoxification of several substances. GSTM1 and GSTT1 are present in the liver in relatively high levels. Polymorphisms of the GSTM1 and GSTT1 genes may affect ligandin functions that are important in bilirubin transportation. OBJECTIVE: The aim of this study was to investigate the role of GSTM1 and GSTT1 gene polymorphisms as risk factors for neonatal jaundice. METHODS: This study was conducted on 72 neonates with pathologic hyperbilirubinemia (bilirubin >15 mg/dL) and 112 neonates with bilirubin level less than 15 mg/dL as a control group. GSTM1 and GSTT1 genotypes were assessed by multiplex polymerase chain reaction. RESULTS: GSTM1 null genotype was significantly higher in the patient compared with control groups (P = 0.005; odds ratio = 2.43; 95% confidence interval, 1.29-4.55) and was significantly associated with higher bilirubin levels compared with the wild genotype (P < 0.001). There was no statistically significant difference in the GSTT1 genotypes between the patient and the control groups. In the patient group, total bilirubin levels did not vary significantly among the null and wild GSTT1 genotypes (P = 0.108). CONCLUSIONS: Neonates with the GSTM1 null genotype are at high risk to develop pathologic hyperbilirubinemia and may have higher bilirubin levels.
