Effects of Senegal haplotype ( Xmn1 -rs7412844), alpha-thalassemia (3.7kb HBA1/HBA2 deletion), NPRL3 -rs11248850 and BCL11A -rs4671393 variants on sickle cell nephropathy.

OBJECTIVE: Sickle cell anemia (SCA) can cause substantial kidney dysfunction resulting in sickle cell nephropathy, which may be affected by the presence of modifier genes. This study evaluates the effects of some modifier genes on sickle cell nephropathy.

METHODS: Patients living with SCA were recruited. Alpha-thalassemia (3.7kb HBA1/HBA2 deletion) was genotyped using gap PCR multiplex. Senegal haplotype (Xmn1-rs7412844), BCL11A -rs4671393 and NPRL3 -rs11248850 were genotyped using Mass Array. The effects of variants on kidney dysfunction were then evaluated using multivariate analysis.

RESULTS: The number of patients living with SCA included in this study was 162 with a median age of 20 years [minimum-maximum: 4-57] and a female frequency of 53.21%. Senegal haplotype, BCL11A -rs4671393 variant were protective factors against albuminuria stage A2 with an odds ratio (OR) of 0.22 (95% CI 0.05-0.90) and 0.27 (95% CI 0.08-0.96) respectively. The combination NPRL3 -rs11248850 variant - 3.7kb HBA1/HBA2 deletion was a protective factor against albuminuria stage A2 ( OR = 0.087, 95% Cl 0.01-0.78) but it was a risk factor for glomerular hyperfiltration ( OR = 17.69, 95% CI 1.85-169.31).

CONCLUSIONS: All four variants displayed a protective effect against albuminuria stage A2. The combination alpha-thalassemia - NPRL3 -rs11248850 variant is a risk factor for glomerular hyperfiltration.