Vitamin D Receptor Gene Polymorphisms Modify Cardiometabolic Response to Vitamin D Supplementation in T2DM Patients

Nasser M Al-Daghri,Majed S Alokail,Abdul Khader Mohammed,Kaiser Wani,Gyanendra Tripathi,Shaun Sabico,Mohammed Ghouse Ahmed Ansari,Syed D Hussain,Omar S Al-Attas

doi:10.1038/s41598-017-08621-7

Nasser M Al-Daghri, Majed S Alokail + Show 7 more

Open Access

https://doi.org/10.1038/s41598-017-08621-7

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Journal: Scientific Reports	Publication Date: Aug 15, 2017
Citations: 35	License type: open-access

Affiliation: King Saud University, University of Westminster

Abstract

There is conflicting evidence on the favorable effects of vitamin D supplementation on metabolic profile in Type 2 diabetes mellitus (T2DM) patients and this might be due to genetic variations in vitamin D receptors (VDRs). Thus, we studied the metabolic effects of a 12-month vitamin D supplementation in T2DM patients according to VDR polymorphisms. A total of 204 T2DM subjects received 2000 IU vitamin D3 daily for 12 months. Serum 25(OH)D and metabolic profiles were measured at baseline and after 12 months. VDR polymorphisms (Taq-I, Bsm-I, Apa-I and Fok-I) were identified using TaqMan genotyping assays. Vitamin D supplementation significantly increased HOMA β-cell function (p = 0.003) as well as significantly decreased triglycerides, total and LDL-cholesterol (p < 0.001). The lowest increment in 25(OH)D levels was detected in patients with Fok-I CC genotypes (p < 0.0001). With vitamin D supplementation, Taq-I GG genotype carriers showed significant improvements in triglycerides, LDL- and total cholesterol, insulin, HbA1c and HOMA-IR (p < 0.005, 0.01, < 0.001, < 0.005, 0.03 and 0.01, respectively). Similarly, Bsm-I TT genotype carriers showed significant improvements in triglycerides (p = 0.01), insulin and HOMA-IR (p-values < 0.05). In conclusion, improvements in metabolic profile due to vitamin D supplementation is influenced by VDR polymorphisms, specifically for carriers of Taq-I GG and Bsm-I TT genotypes.

Highlights

With retinoid X receptor and regulates expression of several target genes[20]
Several single nucleotide polymorphisms (SNPs) have been identified in the vitamin D receptors (VDRs) gene including Taq-I, Bsm-I, and Apa-I polymorphisms, which are located at the 3′ untranslated region (3′ UTR) of the gene and are suspected to alter VDR expression[23, 24]
Since these polymorphisms affect the stability and activity of VDR mRNA and protein, it is likely that the individuals who are not responding cardiometabolically to vitamin D treatment might be due to these VDR SNPs

Summary

Introduction

With retinoid X receptor and regulates expression of several target genes[20]. VDR is expressed in a variety of tissues including muscles and pancreatic cells[21, 22]. Several single nucleotide polymorphisms (SNPs) have been identified in the VDR gene including Taq-I, Bsm-I, and Apa-I polymorphisms, which are located at the 3′ untranslated region (3′ UTR) of the gene and are suspected to alter VDR expression[23, 24]. Fok-I is a functional polymorphism that results in different translation initiation sites on VDR that lead to three amino acids becoming longer and less effective protein[25] Since these polymorphisms affect the stability and activity of VDR mRNA and protein, it is likely that the individuals who are not responding cardiometabolically to vitamin D treatment might be due to these VDR SNPs. recent studies have reported that the VDR genotypes may potentially affect the individual’s response to treatment. 204 T2DM patients who were mostly vitamin D deficient were enrolled and given 2000 IU vitamin D daily for 12 months, and screened for four different VDR SNPs (Taq-I, Bsm-I, Apa-I and Fok-I)

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