Vitamin D receptor gene polymorphisms among Emirati patients with type 2 diabetes mellitus.
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±11.59years and 48.21±12.17years 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.
Faculty of Biomedical Engineering, Khalifa University of Science, Technology & Research, Abu Dhabi, United Arab Emirates; Khalifa University Center of Biotechnology, Abu Dhabi, United Arab Emirates.
Habiba Al
HA
Safar
Khalifa University Center of Biotechnology, Abu Dhabi, United Arab Emirates.
Sarah El Hajj
SEH
Chehadeh
Pathology & Laboratory Medicine Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates.
Laila
L
Abdel-Wareth
VPS Healthcare, Abu Dhabi, United Arab Emirates.
Afrozul
A
Haq
Australian School of Advanced Medicine, Macquarie University, Sydney and School of Community Health, Charles Sturt University, Albury, Australia.
Herbert F
HF
Jelinek
Pathology and Laboratory Medicine Institute, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates.
Gehad
G
ElGhazali
Faculty of Biomedical Engineering, Khalifa University of Science, Technology & Research, Abu Dhabi, United Arab Emirates; College of Natural and Health Sciences, Zayed University, Abu Dhabi, United Arab Emirates. Electronic address: Fatme.AlAnouti@zu.ac.ae.
Fatme Al
FA
Anouti
D000368:Aged; D000483:Alleles; D015992:Body Mass Index; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000097:blood / Q000235:genetics*; D014479:United Arab Emirates / Q000453:epidemiology; D014808:Vitamin D Deficiency / Q000097:blood / Q000150:complications / Q000453:epidemiology / Q000235:genetics*
D008078:Cholesterol, LDL; D018167:Receptors, Calcitriol; C579457:VDR protein, human; D002784:Cholesterol
Gene polymorphism; Type 2 diabetes mellitus; Vitamin D deficiency; Vitamin D receptor