Clinical and genetic associations of renal function and diabetic kidney disease in the United Arab Emirates: a cross-sectional study

Wael M Osman; Herbert F Jelinek; Guan K Tay; Ahsan H Khandoker; Kinda Khalaf; Wael Almahmeed; Mohamed H Hassan; Habiba S Alsafar

doi:10.1136/bmjopen-2017-020759

Clinical and genetic associations of renal function and diabetic kidney disease in the United Arab Emirates: a cross-sectional study

BMJ Open. 2018 Dec 14;8(12):e020759. doi: 10.1136/bmjopen-2017-020759.

Authors

Wael M Osman¹, Herbert F Jelinek^{2

3}, Guan K Tay^{1

4

5

6}, Ahsan H Khandoker⁶, Kinda Khalaf⁶, Wael Almahmeed^{7

8}, Mohamed H Hassan⁹, Habiba S Alsafar^{1

6}

Affiliations

¹ Center of Biotechnology, Khalifa University, Abu Dhabi, United Arab Emirates.
² School of Community Health, Charles Sturt University, Albury, New South Wales, Australia.
³ Clinical Medicine, Macquarie University, Sydney, New South Wales, Australia.
⁴ School of Health and Medical Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.
⁵ School of Psychiatry and Clinical Neurosciences, University of Western Australia, Western Australia, Australia.
⁶ Biomedical Engineering, Khalifa University, Abu Dhabi, United Arab Emirates.
⁷ Institute of Cardiac Science, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates.
⁸ Heart and Vascular Institute, Cleveland Clinic, Abu Dhabi, United Arab Emirates.
⁹ Medical Institute, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates.

Abstract

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 (P_adjusted=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.

Keywords: arab; diabetes; renal; uae.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Cluster Analysis
Cross-Sectional Studies
Diabetic Nephropathies / diagnosis
Diabetic Nephropathies / genetics*
Female
Genetic Association Studies*
Genetic Loci
Genetic Markers / genetics
Genetic Predisposition to Disease / genetics*
Humans
Kidney Function Tests*
Male
Middle Aged
Risk Factors
United Arab Emirates

Substances

Genetic Markers