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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.

Association of ABCB1genetic variants with renal function in Africans and in Caucasians