Molekulare und genetische Medizin

Vitamin D Status and its Receptor Genes BsmI, FokI, ApaI, TaqI Polymorphism in Relation to Glucose Metabolism in Obese Iraqi Type 2 Diabetes Mellitus Patients

Abstract

Al-Darraji SZ, Al-Azzawie HF and Al-Kharsani AR

Background: Vitamin D receptor (VDR) gene polymorphisms are possibly involved in the development of type 2 diabetes mellitus (T2DM). However, the data to date have been inconclusive. Previous studies have suggested an influence of vitamin D receptor alleles on glucose metabolism and on susceptibility to type 2 diabetes mellitus in different ethnic populations through the action of vitamin D endocrine system which related with calcification and lipolysis, insulin secretion, and may be associated with many complicated disease including diabetes. To investigate the relationship between a single nucleotide polymorphism (SNP) of VDR gene and T2DM more studies had been done. However, different results have been found in different spots of the world. Therefore, more studies are needed to understand the variation in these results. This is the first study that shows the implication of the SNP of VDR gene in T2DM in Iraqi patients.

Objective: To assess the correlation between serum 25(OH)D3 levels, and vitamin D receptor (VDR) polymorphisms (Fok1, BsmI, TaqI and ApaI), and glycemic control in obese T2DM Iraqi population, this study was performed.

Materials and methods: 200 clinically diagnosed T2DM patients, distributed into three subgroups according to therapeutic pattern and 75 healthy controls from the Iraqi population were recruited in this study. The association between the VDR gene SNPs and the T2DM was determined using Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique, and genotype and allele frequencies were calculated between the T2DM and control groups.

Results: No significant differences between mean age and the body mass index between both case and control groups were observed. According to current glycemic control consensus, results demonstrated only 20.5 percent of the T2DM patients met this target, which meant that 79.5 percent of the cases were suffering from poor glycemic control 25(OH)D3 levels were significantly lower in the T2DM patients than in the control group, being 17.49 ± 1.12 ng/ml and 31.26 ± 1.25 ng/ml, in the patient and control groups, respectively (p<0.001, Student’s t-test). 25(OH) D3 levels were found to be inversely associated with HbA1c levels in the T2DM patients (p<0.001, r2=0.058). In the group of T2DM patients, 160 of 200 (80 percent) as opposed to 2 of 75 (2.6 percent) in the non-diabetic l group had lower, 25(OH)D3 levels ≤ 20 ng/ml (chi-squared test, p<0.001), while in the group of type 2 patients, 15 of 200 (7.5 percent) as opposed to 5 of 75 (6.6 percent) in the control group, had vitamin D insufficiency, 25(OH)D3 levels > 20 < 30 ng/ml (chi-squared test, p<0.0001). The gene polymorphism analysis for T2DM showed that genotype and alleles frequencies for the VDR genes were in agreement with Hardy–Weinberg equilibrium in all cases.

Conclusion: VDR gene polymorphism analysis revealed that neither genotypes nor alleles of VDR BsmI, ApaI showed a significant variation between T2DM patients and controls. In contrast‚ the FF genotype of VDR FokI and TT genotype of VDR TaqI showed a significant (P<0.0001) increase in T2DM patients in comparison to controls. FF and TT homozygotes had significantly higher baseline fasting glucose and HOMI-IR levels than f allele carriers. In addition, data found significantly elevated interlukin IL-6, TNF-α, IL -1β and decreased osteocalcin in association with the Taq1 polymorphism.