Roles of APOL1G1 and G2 variants in sickle cell disease patients: kidney is the main target

被引：34

作者：

Kormann, Raphael ^{[1
,2
]}

Jannot, Anne-Sophie ^{[2
,3
,4
]}

Narjoz, Celine ^{[2
,5
,6
]}

Ribeil, Jean-Antoine ^{[2
,7
,8
,9
]}

Manceau, Sandra ^{[2
]}

Delville, Marianne ^{[2
,9
]}

Joste, Valentin ^{[2
,5
]}

Prie, Dominique ^{[2
,10
,11
]}

Pouchot, Jacques ^{[2
,12
,13
]}

Thervet, Eric ^{[2
,6
,14
]}

Courbebaisse, Marie ^{[1
,2
,10
]}

Arlet, Jean-Benoit ^{[2
,12
,13
,15
]}

机构：

[1] Georges Pompidou European Hosp, AP HP, Physiol Dept, Paris, France

[2] Paris Descartes Fac Med, Paris, France

[3] INSERM, UMR Informat Sci & Personalized Med E22 1138, Paris, France

[4] Georges Pompidou Univ Hosp, Med Informat Biostat & Publ Hlth Dept, Paris, France

[5] Georges Pompidou Univ Hosp, AP HP, Biochem Dept, Paris, France

[6] INSERM, UMR S 1147, Paris, France

[7] Necker Childrens Hosp, AP HP, Biotherapy Dept, Paris, France

[8] Grp Hosp Univ Ouest, AP HP, Biotherapy Clin Invest Ctr, INSERM, Paris, France

[9] Univ Paris 05, Necker Enfants Malad Univ Hosp, AP HP, Ctr Reference Syndromes Drepanocytaires Majeurs, Paris, France

[10] INSERM, U1151, CNRS, UMR8253, Paris, France

[11] Paris Descartes Univ, Physiol Dept, Necker Childrens Hosp, AP HP, Paris, France

[12] Sorbonne Paris Cite, Sickle Cell Referral Ctr, Fac Med Paris Descartes, Internal Med Dept, Paris, France

[13] Georges Pompidou Univ Hosp, AP HP, Paris, France

[14] Georges Pompidou Univ Hosp, AP HP, Dept Nephrol, Paris, France

[15] Lab Excellence GR Ex, Paris, France

来源：

BRITISH JOURNAL OF HAEMATOLOGY | 2017年 / 179卷 / 02期

关键词：

sickle cell disease; sickle cell nephropathy; APOL1; RISK VARIANTS; PULMONARY-HYPERTENSION; GENETIC-VARIANTS; RENAL-FUNCTION; ADULTS; PROTEIN; PROGRESSION; CHILDREN; ANEMIA; HAPTOGLOBIN;

D O I：

10.1111/bjh.14842

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

In African-American patients with sickle cell disease (SCD), APOL1 G1 and G2 variants are associated with increased risk of sickle cell nephropathy (SCN). To determine the role of APOL1 variants in SCD patients living in Europe, we genotyped 152 SCD patients [aged 30.4 (24 .3-36 .4) years], mainly of Sub-Saharan African ancestry, for APOL1 G1 and G2 and for variants of four genes with kidney tropism (GSTM1, GSTT1, GSTP1, and HMOX1). Homozygous or double-heterozygous APOL G1 and G2 genotypes were strongly associated with end stage renal disease (P = 0.003) and worse Kidney Disease: Improving Global Outcomes stages (P = 0.001). Further, these genotypes were associated in an age-dependent manner with lower estimated glomerular filtration rate (eGFR, P = 0.008), proteinuria (P = 0.009) and albuminuria (P< 0.001) but not with other SCD complications. Compared to APOL1 G1/wild type (WT), the APOL1 G2/WT genotype was associated with a lower eGFR (P = 0.04) in an age-dependent manner, suggesting that the G2/WT patients are likely to have worse kidney prognosis. Other genes variants analysed were not associated with SCN or other SCD complications. Our data indicate that APOL1 screening should be considered for the management of SCD patients, including those of non-African-American origin, as those with homozygous or double heterozygous variants are clearly at higher risk of SCN.

引用

页码：323 / 335

页数：13