Objectives Within the Emirati population, risk factors and genetic predisposition to diabetic kidney disease (DKD) have not yet been investigated. The aim of this research was to determine potential clinical, laboratory and reported genetic loci as risk factors for DKD.
Research design and methods Four hundred and ninety unrelated Emirati nationals with type 2 diabetes mellitus (T2DM) were recruited with and without DKD, and clinical and laboratory data were obtained. Following adjustments for possible confounders, a logistic regression model was developed to test the associations of 63 single nucleotide polymorphisms (SNPs) in 43 genetic loci with DKD (145 patients with DKD and 265 without DKD). Linear regression models, adjusted for age and gender, were then used to study the genetic associations of five renal function traits, including 83 SNPs with albumin-to-creatinine ratio, 92 SNPs with vitamin D (25-OH cholecalciferol), 288 SNPs with estimated glomerular filtration rate (eGFR), 363 SNPs with serum creatinine and 73 SNPs with blood urea.
Results Patients with DKD, as compared with those without the disease, were mostly men (52%vs38% for controls), older (67vs59 years) and had significant rates of hypertension and dyslipidaemia. Furthermore, patients with DKD had T2DM for a longer duration of time (16vs10 years), which in an additive manner was the single factor that significantly contributed to the development of DKD (p=0.02, OR=3.12, 95% CI 1.21 to 8.02). Among the replicated associations of the genetic loci with different renal function traits, the most notable included SHROOM3 with levels of serum creatinine, eGFR and DKD (Padjusted=0.04, OR=1.46); CASR, GC and CYP2R1 with vitamin D levels; as well as WDR72 with serum creatinine and eGFR levels.
Conclusions Associations were found between several genetic loci and risk markers for DKD, which may influence kidney function traits and DKD in a population of Arab ancestry.
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Patient consent for publication Obtained.
Contributors HSA obtained the funding for this study. WMO, HSA and HFJ designed the study. WMO analyzed the data and prepared the manuscript. HFJ, GKT, AHK, and KK provided critical revision of the manuscript, contributed to writing the discussion, and writing the revisionof the manuscript. WA and MHH carried out the patient recruitment process and acquired the clinical data. All authors gave final approval of the version to be published.
Funding This study was supported by research incentive funds from Khalifa University Internal Research Fund Level 2 granted to HSA.
Competing interests None declared.
Ethics approval The study was approved by the Institutional Ethics Committees of both local hospitals (REC-04062014 and R292, respectively).
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement No additional data are available.
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