<i>APOL1</i>
            , α-thalassemia, and
            <i>BCL11A</i>
            variants as a genetic risk profile for progression of chronic kidney disease in sickle cell anemia

Saraf, Santosh L.; Shah, Binal N.; Xu, Zu-De; Han, Jin; Tayo, Bamidele O.; Abbasi, Taimur; Ostrower, Adam; Guzmán, Elizabeth Hernández; Molokie, Robert E.; Gowhari, Michel; Hassan, Johara; Jain, Shivi; Cooper, Richard S.; Machado, Roberto F.; Lash, James P.; Gordeuk, Victor R.

doi:10.3324/haematol.2016.154153

Cited by 48 publications

(65 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The significant association of variants at APOL1 and nearsignificant association of HMOX1 rs743811 with crude albuminuria or eGFR, both early indicators of renal dysfunction, are novel findings requiring further investigation in more adult Cameroonian SCD patients. In total, the present study indicates that the 3Á7 kb HBA1/HBA2 deletion, HMOX1 and APOL1G1/G2 polymorphisms, in addition to other variants, such as HbF-promoting loci (Saraf et al, 2017), and variants that still need validations (Schaefer et al, 2016), could lead to early identification of high-risk SCD patients, and contribute to a better screening strategies, leading to targeted preventive and therapeutic interventions.…”

Section: Discussionmentioning

confidence: 75%

Clinical and genetic predictors of renal dysfunctions in sickle cell anaemia in Cameroon

et al. 2017

View full text Add to dashboard Cite

SUMMARY Micro-albuminuria and glomerular hyperfiltration are primary indicators of renal dysfunctions in Sickle Cell Disease (SCD), with more severe manifestations previously associated with variants in APOL1 and HMOX1 among African Americans. We have investigated 413 SCD patients from Cameroon. Anthropometric variables, haematological indices, crude albuminuria, albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) were measured. Patients were genotyped for 3.7 kB alpha-globin gene (HBA1/HBA2) deletion, and for variants in APOL1 (G1/G2; rs60910145, rs73885319, rs71785313) and HMOX1 (rs3074372, rs743811). The median age was 15 years; the majority presented with micro-albuminuria (60.9%; n = 248), and approximately half with glomerular hyperfiltration (49.5%; n = 200). Age, male sex, haemoglobin level, leucocyte count, mean corpuscular volume, blood pressure, body mass index and creatinine levels significantly affected albuminuria and/or eGFR. Co-inheritance of alpha-thalassaemia was protective against macro-albuminuria (p = 0.03). APOL1 G1/G2 risk variants were significantly associated with the ACR (p = 0.01) and borderline with eGFR (p = 0.07). HMOX1 - rs743811 was borderline associated with micro-albuminuria (p = 0.07) and macro-albuminuria (p = 0.06). The results revealed a high proportion of micro-albuminuria and glomerular hyperfiltration among Cameroonian SCD patients, and support the possible use of targeted genetic biomarkers for risks assessment.

show abstract

Section: Discussionmentioning

confidence: 75%

Clinical and genetic predictors of renal dysfunctions in sickle cell anaemia in Cameroon

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Little evidence links increased fetal hemoglobin and renal dysfunction; in one longitudinal study of 725 SCD patients, the CAR β s haplotype was associated with a high risk of renal failure [66], and in another study of 144 children with SCA, higher hemoglobin F levels were associated with lower prevalence of microalbuminuria [67]. A common BCL11A polymorphism was also associated with lower albumin/creatinine ratio (ACR) than wild type in an adult cohort of SCD [68]. Studies evaluating the effect of hemoglobin F levels on SCT-related nephropathy, however, have not yet been performed.…”

Section: Modifying Factorsmentioning

confidence: 99%

“…In SCD, APOL1 high-risk variants were associated with a 3-fold increased risk of proteinuria by dipstick measure but not eGFR in one study of 521 patients [73]. Another study of 262 adults with SCA demonstrated an association of APOL1 high-risk variants with albuminuria and renal progression (defined as 50% decline in eGFR or ESRD) [68]. …”

Section: Modifying Factorsmentioning

confidence: 99%

The spectrum of sickle hemoglobin-related nephropathy: from sickle cell disease to sickle trait

Naik

Derebail

2017

Expert Review of Hematology

View full text Add to dashboard Cite

Introduction Renal dysfunction is among the most common complication of sickle cell disease (SCD), from hyposthenuria in children to progression to overt chronic kidney disease (CKD) in young adults. Emerging evidence now suggests that sickle hemoglobin-related nephropathy extends to individuals with sickle cell trait (SCT). Areas covered This review will highlight the pathophysiology, epidemiology, and management recommendations for sickle hemoglobin-related nephropathy in both SCD and SCT. In addition, it will focus on the major demographic and genetic modifiers of renal disease in sickling hemoglobinopathies. Expert commentary Studies have elucidated the course of renal disease in SCD; however, the scope and age of onset of renal dysfunction in SCT has yet to be determined. In SCD, several modifiers of renal disease – such as α-thalassemia, hemoglobin F, APOL1 and HMOX1 – have been described and provide an opportunity for a precision medicine approach to risk stratify patients who may benefit from early intervention. Extrapolating from this literature may also provide insight into the modifiers of renal disease in SCT. Further studies are needed to determine the optimal treatment for sickle hemoglobin-related nephropathy.

show abstract

“…Biomarkers of SCD severity, including fetal Hb level and hemolysis indices have a high heritability and numerous genetic variants are associated with these traits . Organ‐specific problems, such as sickle nephropathy and susceptibility to red blood cell alloimmunization are influenced by genetic information that will likely be used prospectively for therapeutic decisions. We use pharmacogenetics data routinely to guide codeine use in SCD .…”

Section: Discussionmentioning

confidence: 99%

Sickle Cell Clinical Research and Intervention Program (SCCRIP): A lifespan cohort study for sickle cell disease progression from the pediatric stage into adulthood

Hankins

Estepp

Hodges

et al. 2018

Pediatric Blood & Cancer

View full text Add to dashboard Cite

show abstract

APOL1 , α-thalassemia, and BCL11A variants as a genetic risk profile for progression of chronic kidney disease in sickle cell anemia

Cited by 48 publications

References 15 publications

Clinical and genetic predictors of renal dysfunctions in sickle cell anaemia in Cameroon

Clinical and genetic predictors of renal dysfunctions in sickle cell anaemia in Cameroon

The spectrum of sickle hemoglobin-related nephropathy: from sickle cell disease to sickle trait

Sickle Cell Clinical Research and Intervention Program (SCCRIP): A lifespan cohort study for sickle cell disease progression from the pediatric stage into adulthood

Contact Info

Product

Resources

About