A study for the role of apolipoprotein-1 gene haplotypes as a genetic predictor of renal dysfunction among pediatric Egyptian sickle cell disease patients

Background
Sickle cell nephropathy (SCN) is linked with significant morbidity and mortality. SCN is first presented as glomerular hyperfiltration then it progresses to focal segmental glomerular sclerosis, and eventually, renal failure.


Aim
Determination of the prevalence of apolipoprotein-1 (APOL-1) polymorphisms among sickle cell disease Egyptian pediatric patients and its role as a genetic predictor of renal dysfunction.


Patients and methods
A total of 69 patients with sickle cell anemia, 28 S/β thalassemia, and three sickle trait patients underwent full history taking, examination, laboratory tests, and DNA analysis for APOL-1 G1 single-nucleotide polymorphisms S342G and I384M using PCR-restriction fragment length polymorphism analysis.


Results

The prevalence of APOL-1 G1 variants among our patients was 44%, 23% of them had G1
GM
subhaplotype and 77% had G1
G+
subhaplotype. Among 17 cases of microalbuminuria, (53%) had G1 variants. Hyperfiltration cases were 10 cases of which seven (70%) cases had the G1 variants. out of the 30 cases of mildly decreased estimated glomerular filtration rate (eGFR) (43.3%) had G1 variants and the two cases of mild to moderately decreased eGFR (100%) had G1 variant; the G1
GM
subhaplotype. A significant association was found between G1
GM
subhaplotype and later stages of chronic kidney disease; as microalbuminuria (
P
=0.026) and mildly to moderately decreased eGFR (
P
=0.020).



Conclusion

APOL-1 risk variant G1
GM
was associated with more severe stages of chronic kidney disease, indicating a more prominent association with SCN progression.