Association of Angiotensin-converting enzyme (ACE) genetic variants with nephropathy in sickle cell disease: evidence from an Egyptian cohort

Background Sickle cell disease (SCD) patients suffer nephropathy with acute decline in estimated glomerular filtration rate show higher mortality rates. Early identification of at-risk patients can enable efficient management. Sickle cell nephropathy (SCN) pathophysiology is multifactorial, with involvement of several genetic modifiers in its progression. Angiotensin-converting enzyme (ACE) gene variations have been linked to several conditions, including nephropathy. Purpose This study aims to explore the potential association of ACE gene single-nucleotide variant (single nucleotide variant rs1800764) and insertion/deletion (rs4340) genetic variant with SCN in a cohort of Egyptian SCD patients. Patients and methods ACE (rs4340) and (rs1800764) genotyping was performed for 100 SCD patients and 100 healthy age-gender-matched volunteers as a control group using the PCR-restriction fragment length polymorphism technique. Results ACE (rs1800764) polymorphic genotypes (TC and TT) were significantly more frequent among SCD patients compared with controls ( P =0.005). The homomutant ACE genotype (TT) was significantly association with microalbuminuria ( P =0.048) as well as loin pain ( P =0.011). In the studied cohort, ACE (rs4340) variant shows no association with nephropathy risk. However, individuals with the I/D genotype had more frequent emergency admission compared with those with I/I ( P =0.004) or D/D ( P =0.047) genotypes. The genotype distribution of ACE (rs4340) in patients was similar to that observed in the control group. Conclusion The mutated ACE gene variant rs1800764 has been linked to SCN and may serve as a predictive genetic marker. Additionally, the rs4340 insertion/deletion (I/D) variant of the ACE gene has shown a significant association with emergency hospital admissions in SCD patients.