Association of <it>ABCB1 </it>genetic variants with renal function in Africans and in Caucasians

• Main Authors: Elston Robert C (Author), Bergmann Sven (Author), Bovet Pascal (Author), Vollenweider Peter (Author), Johnson Toby (Author), Maillard Marc (Author), Eap Chin B (Author), Bochud Murielle (Author), Beckmann Jacques S (Author), Waterworth Dawn M (Author), Mooser Vincent (Author), Gabriel Anne (Author), Burnier Michel (Author)
• Format: Book
• Published: BMC, 2008-06-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

<p>Abstract</p> <p>Background</p> <p>The P-glycoprotein, encoded by the <it>ABCB1 </it>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 <it>ABCB1 </it>variants with renal function in African and Caucasian subjects.</p> <p>Methods</p> <p>In Africans (290 subjects from 62 pedigrees), we genotyped the <it>2677G>T </it>and <it>3435 C>T ABCB1 </it>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 <it>ABCB1</it>, 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.</p> <p>Results</p> <p>In Africans, compared to the reference genotype (GG or CC), each copy of the <it>2677T </it>and <it>3435T </it>allele was associated, respectively, with: GFR higher by 10.6 ± 2.9 (<it>P </it>< 0.001) and 4.4 ± 2.3 (<it>P </it>= 0.06) mL/min; ERPF higher by 47.5 ± 11.6 (<it>P </it>< 0.001) and 28.1 ± 10.5 (<it>P </it>= 0.007) mL/min; and renal resistances lower by 0.016 ± 0.004 (<it>P </it>< 0.001) and 0.011 ± 0.004 (<it>P </it>= 0.004) mm Hg/mL/min. In Caucasians, we identified 3 polymorphisms in the <it>ABCB1 </it>gene that were strongly associated with all estimates of GFR (smallest P value = 0.0006, overall P = 0.014 after multiple testing correction).</p> <p>Conclusion</p> <p>Variants of the <it>ABCB1 </it>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.</p>

Item Description

10.1186/1755-8794-1-21
1755-8794