Genetic Association between the Endothelial Nitric Oxide Synthase Gene Polymorphism (T786C) and Nephropathy in Sudanese Sickle Cell Disease Patients in Khartoum State

Abstract

Background: Sickle cell nephropathy (SCN) is one of the major cause of morbidity and mortality among patients with sickle cell disease (SCD), arising from chronic hemolysis, oxidative stress, and endothelial dysfunction. Variations in the endothelial nitric oxide synthase (eNOS) gene may influence nitric oxide (NO) bioavailability, potentially affecting renal susceptibility in SCD.
Aim: This study aimed to detect the association of eNOS gene polymorphism (T786C) with nephropathy among Sudanese patients with SCD.
Method: A case-control study was conducted between June 2021 and June 2022 at Soba University Hospital and Jafar Ibn Auf Specialized Hospital, Khartoum. 155 Participants included (65 patients with sickle cell nephropathy, two control groups 45 nephropathy patients without SCD, and 45 healthy controls). Samples were used for CBC and DNA extraction (RBCs, Hb, P CV, PLTs, WBCs, RBC count, and RBC indices): Was done using an automated hematology analyzer. Genomic DNA was extracted from blood samples and analyzed for T786C polymorphisms using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) techniques. Statistical assessment was carried out with a statistical package for the social sciences (SPSS), including Chi-square analysis and logistic regression.
Result: The NOS3 (T786C) genotype distributions differed significantly between SCD nephropathy cases and healthy controls (X² = 5.973, p = 0.050). The C allele of T786C was significantly more frequent among cases (p = 0.004). Logistic regression revealed a strong association of the T786C polymorphism with nephropathy under the dominant model, where carriers of at least one C allele (T/C+C/C) had increased risk compared to T/T carriers (OR = 8.96, 95%CI:1.11–72.14, p = 0.039). Genotype distribution of the normal control group predominantly exhibited the T/T genotype (97.8%), p = 0.050, with only1individual (2.2%) carryingtheT/Cgenotype, p = 0.050, and none with C/C, p = 0.050. The abnormal control group had 41 individuals (91.1%) with the T/T genotype, p = 0.050, 3 (6.7%) with T/C, p = 0.050, and 1 (2.2%) with C/C, p = 0.050. Hematological parameters showed no genotype- related variations.
Conclusion: eNOS T786C polymorphism appears to be associated with increased susceptibility to nephropathy among Sudanese SCD patients, suggesting a role for endothelial nitric oxide pathway dysfunction in the pathogenesis of sickle cell nephropathy.
The limitation faced is the sample size, which is sufficient to detect associations in dominant genetic models, but may lack the statistical power to capture subtle effects of less frequent genotypes.