Vitamin D receptor gene polymorphisms among Emirati patients with type 2 diabetes mellitus

Habiba S. Al Safar, Sarah El Hajj Chehadeh, Laila Abdel-Wareth, Afrozul Haq, Herbert F. Jelinek, Gehad ElGhazali, Fatme Al Anouti

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

At a prevalence rate close to 19.5%, the UAE has one of the highest rates of Type 2 Diabetes Mellitus (T2DM) in the world. Genome wide association studies (GWAS) have led to the identification of several genetic variants that are associated with T2DM. Recently, genes involved in vitamin D metabolism have gained interest because of the association between vitamin D deficiency (VDD) and increased risk for T2DM. Among these, the Vitamin D receptor (VDR) gene is a good candidate for T2DM susceptibility. The aim of this study was to investigate the association between VDR polymorphisms and T2DM among a representative sample of the Emirati population. In this cross sectional study, two hundred and sixty four patients with T2DM and ninety-one healthy controls were enrolled. The study population was genotyped for the three VDR gene mutations, TaqI (rs731236), FokI (rs2228570) and BsmI (rs1544410). VDR alleles and haplotypes were compared between patients and their healthy controls. The mean age of the T2DM cohort was 60. ±. 11.59. years and 48.21. ±. 12.17. years for the healthy controls. The G-allele and GG genotype of rs2228570 and T-allele and TT genotype of rs1544410 SNPs were associated with T2DM. In regards to T2DM-related metabolic complications, the AG and GG genotypes of rs731236 were significantly associated with higher total cholesterol (p = 0.011) and LDL-cholesterol (p = 0.009) levels in the patients with T2DM. In contrast, the CT genotype of rs1544410 was significantly associated with lower BMI (p = 0.031) and the TT genotype was associated with lower LDL-cholesterol level (p = 0.007). The frequency of AAT and GGC haplotypes was also different between groups (p = 0.014; p = 0.032, respectively), implying that these haplotypes of the VDR gene are associated with the susceptibility to T2DM in the Emirati population. To conclude, an association between SNPs in the VDR gene (except for rs731236) and T2DM per se was demonstrated. The rs731236 variant was shown to be associated with high cholesterol and LDL-cholesterol levels in T2DM patients, while rs1544410 was associated with lower BMI and lower LDL cholesterol levels. Our results imply that alleles and haploypes of the VDR gene are associated with the susceptibility to T2DM in the Emirati population.
Original languageEnglish
Pages (from-to)119-124
Number of pages6
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume175
DOIs
Publication statusPublished - 2018

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Calcitriol Receptors
Medical problems
Polymorphism
Type 2 Diabetes Mellitus
Genes
LDL Cholesterol
Genotype
Alleles
Haplotypes
Vitamin D
Population
Single Nucleotide Polymorphism
Cholesterol
Vitamin D Deficiency
Genome-Wide Association Study
Metabolism

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Al Safar, Habiba S. ; Chehadeh, Sarah El Hajj ; Abdel-Wareth, Laila ; Haq, Afrozul ; Jelinek, Herbert F. ; ElGhazali, Gehad ; Anouti, Fatme Al. / Vitamin D receptor gene polymorphisms among Emirati patients with type 2 diabetes mellitus. In: Journal of Steroid Biochemistry and Molecular Biology. 2018 ; Vol. 175. pp. 119-124.
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abstract = "At a prevalence rate close to 19.5{\%}, the UAE has one of the highest rates of Type 2 Diabetes Mellitus (T2DM) in the world. Genome wide association studies (GWAS) have led to the identification of several genetic variants that are associated with T2DM. Recently, genes involved in vitamin D metabolism have gained interest because of the association between vitamin D deficiency (VDD) and increased risk for T2DM. Among these, the Vitamin D receptor (VDR) gene is a good candidate for T2DM susceptibility. The aim of this study was to investigate the association between VDR polymorphisms and T2DM among a representative sample of the Emirati population. In this cross sectional study, two hundred and sixty four patients with T2DM and ninety-one healthy controls were enrolled. The study population was genotyped for the three VDR gene mutations, TaqI (rs731236), FokI (rs2228570) and BsmI (rs1544410). VDR alleles and haplotypes were compared between patients and their healthy controls. The mean age of the T2DM cohort was 60. ±. 11.59. years and 48.21. ±. 12.17. years for the healthy controls. The G-allele and GG genotype of rs2228570 and T-allele and TT genotype of rs1544410 SNPs were associated with T2DM. In regards to T2DM-related metabolic complications, the AG and GG genotypes of rs731236 were significantly associated with higher total cholesterol (p = 0.011) and LDL-cholesterol (p = 0.009) levels in the patients with T2DM. In contrast, the CT genotype of rs1544410 was significantly associated with lower BMI (p = 0.031) and the TT genotype was associated with lower LDL-cholesterol level (p = 0.007). The frequency of AAT and GGC haplotypes was also different between groups (p = 0.014; p = 0.032, respectively), implying that these haplotypes of the VDR gene are associated with the susceptibility to T2DM in the Emirati population. To conclude, an association between SNPs in the VDR gene (except for rs731236) and T2DM per se was demonstrated. The rs731236 variant was shown to be associated with high cholesterol and LDL-cholesterol levels in T2DM patients, while rs1544410 was associated with lower BMI and lower LDL cholesterol levels. Our results imply that alleles and haploypes of the VDR gene are associated with the susceptibility to T2DM in the Emirati population.",
keywords = "Gene polymorphism, Type 2 diabetes mellitus, Vitamin D deficiency, Vitamin D receptor",
author = "{Al Safar}, {Habiba S.} and Chehadeh, {Sarah El Hajj} and Laila Abdel-Wareth and Afrozul Haq and Jelinek, {Herbert F.} and Gehad ElGhazali and Anouti, {Fatme Al}",
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Vitamin D receptor gene polymorphisms among Emirati patients with type 2 diabetes mellitus. / Al Safar, Habiba S.; Chehadeh, Sarah El Hajj; Abdel-Wareth, Laila; Haq, Afrozul; Jelinek, Herbert F.; ElGhazali, Gehad; Anouti, Fatme Al.

In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 175, 2018, p. 119-124.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Vitamin D receptor gene polymorphisms among Emirati patients with type 2 diabetes mellitus

AU - Al Safar, Habiba S.

AU - Chehadeh, Sarah El Hajj

AU - Abdel-Wareth, Laila

AU - Haq, Afrozul

AU - Jelinek, Herbert F.

AU - ElGhazali, Gehad

AU - Anouti, Fatme Al

PY - 2018

Y1 - 2018

N2 - At a prevalence rate close to 19.5%, the UAE has one of the highest rates of Type 2 Diabetes Mellitus (T2DM) in the world. Genome wide association studies (GWAS) have led to the identification of several genetic variants that are associated with T2DM. Recently, genes involved in vitamin D metabolism have gained interest because of the association between vitamin D deficiency (VDD) and increased risk for T2DM. Among these, the Vitamin D receptor (VDR) gene is a good candidate for T2DM susceptibility. The aim of this study was to investigate the association between VDR polymorphisms and T2DM among a representative sample of the Emirati population. In this cross sectional study, two hundred and sixty four patients with T2DM and ninety-one healthy controls were enrolled. The study population was genotyped for the three VDR gene mutations, TaqI (rs731236), FokI (rs2228570) and BsmI (rs1544410). VDR alleles and haplotypes were compared between patients and their healthy controls. The mean age of the T2DM cohort was 60. ±. 11.59. years and 48.21. ±. 12.17. years for the healthy controls. The G-allele and GG genotype of rs2228570 and T-allele and TT genotype of rs1544410 SNPs were associated with T2DM. In regards to T2DM-related metabolic complications, the AG and GG genotypes of rs731236 were significantly associated with higher total cholesterol (p = 0.011) and LDL-cholesterol (p = 0.009) levels in the patients with T2DM. In contrast, the CT genotype of rs1544410 was significantly associated with lower BMI (p = 0.031) and the TT genotype was associated with lower LDL-cholesterol level (p = 0.007). The frequency of AAT and GGC haplotypes was also different between groups (p = 0.014; p = 0.032, respectively), implying that these haplotypes of the VDR gene are associated with the susceptibility to T2DM in the Emirati population. To conclude, an association between SNPs in the VDR gene (except for rs731236) and T2DM per se was demonstrated. The rs731236 variant was shown to be associated with high cholesterol and LDL-cholesterol levels in T2DM patients, while rs1544410 was associated with lower BMI and lower LDL cholesterol levels. Our results imply that alleles and haploypes of the VDR gene are associated with the susceptibility to T2DM in the Emirati population.

AB - At a prevalence rate close to 19.5%, the UAE has one of the highest rates of Type 2 Diabetes Mellitus (T2DM) in the world. Genome wide association studies (GWAS) have led to the identification of several genetic variants that are associated with T2DM. Recently, genes involved in vitamin D metabolism have gained interest because of the association between vitamin D deficiency (VDD) and increased risk for T2DM. Among these, the Vitamin D receptor (VDR) gene is a good candidate for T2DM susceptibility. The aim of this study was to investigate the association between VDR polymorphisms and T2DM among a representative sample of the Emirati population. In this cross sectional study, two hundred and sixty four patients with T2DM and ninety-one healthy controls were enrolled. The study population was genotyped for the three VDR gene mutations, TaqI (rs731236), FokI (rs2228570) and BsmI (rs1544410). VDR alleles and haplotypes were compared between patients and their healthy controls. The mean age of the T2DM cohort was 60. ±. 11.59. years and 48.21. ±. 12.17. years for the healthy controls. The G-allele and GG genotype of rs2228570 and T-allele and TT genotype of rs1544410 SNPs were associated with T2DM. In regards to T2DM-related metabolic complications, the AG and GG genotypes of rs731236 were significantly associated with higher total cholesterol (p = 0.011) and LDL-cholesterol (p = 0.009) levels in the patients with T2DM. In contrast, the CT genotype of rs1544410 was significantly associated with lower BMI (p = 0.031) and the TT genotype was associated with lower LDL-cholesterol level (p = 0.007). The frequency of AAT and GGC haplotypes was also different between groups (p = 0.014; p = 0.032, respectively), implying that these haplotypes of the VDR gene are associated with the susceptibility to T2DM in the Emirati population. To conclude, an association between SNPs in the VDR gene (except for rs731236) and T2DM per se was demonstrated. The rs731236 variant was shown to be associated with high cholesterol and LDL-cholesterol levels in T2DM patients, while rs1544410 was associated with lower BMI and lower LDL cholesterol levels. Our results imply that alleles and haploypes of the VDR gene are associated with the susceptibility to T2DM in the Emirati population.

KW - Gene polymorphism

KW - Type 2 diabetes mellitus

KW - Vitamin D deficiency

KW - Vitamin D receptor

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