Research article

Association of ABCB1 genetic variants with renal function in Africans and in Caucasians

Murielle Bochud¹ , Chin B Eap² , Marc Maillard³ , Toby Johnson^1,4,5 , Peter Vollenweider⁶ , Pascal Bovet^1,7 , Robert C Elston⁸ , Sven Bergmann^4,5 , Jacques S Beckmann^4,9 , Dawn M Waterworth¹⁰ , Vincent Mooser¹⁰ , Anne Gabriel⁷ and Michel Burnier³

¹University Institute of Social and Preventive Medicine (IUMSP), Centre Hospitalier Universitaire Vaudois and University of Lausanne, Bugnon 17, Lausanne, Switzerland

²Unit of Biochemistry and Clinical Psychopharmacology, Center for Psychiatric Neurosciences, Department of Psychiatry, Centre Hospitalier Universitaire Vaudois and University of Lausanne Lausanne, Switzerland

³Division of Nephrology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland

⁴Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland

⁵Swiss Institute of Bioinformatics, Lausanne, Switzerland

⁶Department of Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland

⁷Ministry of Health, Victoria, Seychelles

⁸Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland (OH), USA

⁹Service of Medical Genetics, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland

¹⁰Division of Genetics, GlaxoSmithKline, Philadelphia, Pennsylvania, USA

author email corresponding author email

BMC Medical Genomics 2008, 1:21doi:10.1186/1755-8794-1-21

Published:	2 June 2008

Abstract

Background

The P-glycoprotein, encoded by the ABCB1 gene, is expressed in human endothelial and mesangial cells, which contribute to control renal plasma flow and glomerular filtration rate. We investigated the association of ABCB1 variants with renal function in African and Caucasian subjects.

Methods

In Africans (290 subjects from 62 pedigrees), we genotyped the 2677G>T and 3435 C>T ABCB1 polymorphisms. Glomerular filtration rate (GFR) was measured using inulin clearance and effective renal plasma flow (ERPF) using para-aminohippurate clearance. In Caucasians (5382 unrelated subjects), we analyzed 30 SNPs located within and around ABCB1, using data from the Affymetrix 500 K chip. GFR was estimated using the simplified Modification of the Diet in Renal Disease (MDRD) and Cockcroft-Gault equations.

Results

In Africans, compared to the reference genotype (GG or CC), each copy of the 2677T and 3435T allele was associated, respectively, with: GFR higher by 10.6 ± 2.9 (P < 0.001) and 4.4 ± 2.3 (P = 0.06) mL/min; ERPF higher by 47.5 ± 11.6 (P < 0.001) and 28.1 ± 10.5 (P = 0.007) mL/min; and renal resistances lower by 0.016 ± 0.004 (P < 0.001) and 0.011 ± 0.004 (P = 0.004) mm Hg/mL/min. In Caucasians, we identified 3 polymorphisms in the ABCB1 gene that were strongly associated with all estimates of GFR (smallest P value = 0.0006, overall P = 0.014 after multiple testing correction).

Conclusion

Variants of the ABCB1 gene were associated with renal function in both Africans and Caucasians and may therefore confer susceptibility to nephropathy in humans. If confirmed in other studies, these results point toward a new candidate gene for nephropathy in humans.