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

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

^*Corresponding author for this work

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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=002, OR=312, 95% CI 121 to 802) 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 =004, OR=146); 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.

Original language	English
Article number	e020759
Pages (from-to)	1-9
Number of pages	9
Journal	BMJ Open
Volume	8
Issue number	12
DOIs	https://doi.org/10.1136/bmjopen-2017-020759
Publication status	Published - 1 Dec 2018

Bibliographical note

Copyright the Author(s) 2018. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

Arab
Diabetes
Renal
Uae

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10.1136/bmjopen-2017-020759

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@article{e2e4df06d4014a56b19c0787332d9a7f,

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

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=002, OR=312, 95% CI 121 to 802) 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 =004, OR=146); 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",

author = "Osman, {Wael M.} and Jelinek, {Herbert F.} and Tay, {Guan K.} and Khandoker, {Ahsan H.} and Kinda Khalaf and Wael Almahmeed and Hassan, {Mohamed H.} and Alsafar, {Habiba S.}",

note = "Copyright the Author(s) 2018. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.",

year = "2018",

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day = "1",

doi = "10.1136/bmjopen-2017-020759",

language = "English",

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T1 - Clinical and genetic associations of renal function and diabetic kidney disease in the United Arab Emirates

T2 - a cross-sectional study

AU - Osman, Wael M.

AU - Jelinek, Herbert F.

AU - Tay, Guan K.

AU - Khandoker, Ahsan H.

AU - Khalaf, Kinda

AU - Almahmeed, Wael

AU - Hassan, Mohamed H.

AU - Alsafar, Habiba S.

N1 - Copyright the Author(s) 2018. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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=002, OR=312, 95% CI 121 to 802) 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 =004, OR=146); 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.

AB - 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=002, OR=312, 95% CI 121 to 802) 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 =004, OR=146); 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.

KW - Arab

KW - Diabetes

KW - Renal

KW - Uae

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

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