Journal Article

Estimated glomerular filtration rate and its association with the retinol-binding protein 4 (<i>RBP4</i>) locus on human chromosome 10q23

Daniel P.K. Ng, Agus Salim, Xiu-Li Lim and Siti Nurbaya

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 27, issue 4, pages 1511-1515
Published in print April 2012 | ISSN: 0931-0509
Published online August 2011 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfr442
Estimated glomerular filtration rate and its association with the retinol-binding protein 4 (RBP4) locus on human chromosome 10q23

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Background. We tested for associations between estimated glomerular filtration rate (eGFR) and retinol-binding protein 4 (RBP4) haplotypes found on human chromosome 10q23. This locus had been linked to eGFR in a previous linkage scan in patients with Type 2 diabetes mellitus.

Methods. We analysed 469 patients with Type 2 diabetes and 174 normoalbuminuric controls for associations between RBP4 haplotypes and eGFR. For comparison with controls, 295 cases with proteinuria/end-stage renal disease were tested for associations with advanced diabetic nephropathy. Genotyping was performed using high-resolution DNA melting assays. Data analysis was performed using the haplo.stats package.

Results. Genetic variations in RBP4 were not associated with advanced diabetic nephropathy. Compared with the common A/G/G/C haplotype, C/A/A/C carriers among the normoalbuminuric controls had higher eGFR values among younger patients but lower eGFRs among the older patients (effect size = 2.2, P = 3.3 × 10−7). Furthermore, while eGFR values were fairly consistent over the range of systolic blood pressure (SBP) values for the common haplotype, eGFR in C/A/A/C carriers increased with SBP (effect size = 3.6, P = 1.5 × 10−2). There was a significant interaction between the C/A/A/C haplotype and HbA1c as they affect eGFR compared to the common haplotype (effect size = 2.1, P = 2.1 × 10−3). Power calculations demonstrated that our study had >90% power to detect the observed interactions even while performing multiple hypotheses testing. The interaction between SBP and the C/A/A/C haplotype remained significant (P = 2.8 × 10−2) even when these three haplotype–environment interactions were simultaneously estimated.

Conclusion. RBP4 haplotypes may be important in genetically modulating renal function in response to environmental challenges among patients with Type 2 diabetes.

Keywords: estimated glomerular filtration rate; haplotypes; interaction; multiple hypothesis testing; retinol-binding protein 4

Journal Article.  3375 words. 

Subjects: Nephrology

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