title: Estimated glomerular filtration rate and its association with the retinol-binding protein 4 (RBP4) locus on human chromosome 10q23.
abstract: 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.
  
  
  CONCLUSIONS
  RBP4 haplotypes may be important in genetically modulating renal function in response to environmental challenges among patients with Type 2 diabetes.
authors.affiliation: Department of Epidemiology and Public Health, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. ephnpkd@nus.edu.sg
authors.forename: Daniel P K
authors.initials: DP
authors.lastname: Ng
authors.forename: Agus
authors.initials: A
authors.lastname: Salim
authors.forename: Xiu-Li
authors.initials: XL
authors.lastname: Lim
authors.forename: Siti
authors.initials: S
authors.lastname: Nurbaya
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D015331:Cohort Studies; D048909:Diabetes Complications / Q000209:etiology; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000209:etiology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007676:Kidney Failure, Chronic / Q000209:etiology; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011507:Proteinuria / Q000209:etiology; D054839:Retinol-Binding Proteins, Plasma / Q000235:genetics*
chemical_list: C101326:RBP4 protein, human; D054839:Retinol-Binding Proteins, Plasma