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

Nephrol Dial Transplant. 2012 Apr;27(4):1511-5. doi: 10.1093/ndt/gfr442. Epub 2011 Aug 5.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Chromosomes, Human, Pair 10 / genetics*
  • Cohort Studies
  • Diabetes Complications / etiology
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Diabetic Nephropathies / etiology
  • Female
  • Genetic Predisposition to Disease*
  • Genotype
  • Haplotypes / genetics
  • Humans
  • Kidney Failure, Chronic / etiology
  • Linkage Disequilibrium
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Prognosis
  • Proteinuria / etiology
  • Retinol-Binding Proteins, Plasma / genetics*


  • RBP4 protein, human
  • Retinol-Binding Proteins, Plasma