Relationship of four vitamin D receptor gene polymorphisms with type 1 diabetes mellitus susceptibility in Kuwaiti children

Hessa Al-Kandari,Majedah A Rasoul,Maria Al-Mahdi,Mohammad Z Haider,Gursev S Dhaunsi

doi:10.1186/s12887-019-1448-0

Abstract

BackgroundThe incidence of type 1 diabetes mellitus (T1DM) in Kuwait is amongst the highest in the world. Vitamin D is considered to be involved in immune modulation and its deficiency contribute to autoimmune destruction of insulin producing beta cells in T1DM patients. Vitamin D has been shown to exert its effects via a nuclear vitamin D receptor (VDR) and therefore, VDR gene may be considered a candidate for T1DM susceptibility.MethodsThe genotypes of four VDR gene polymorphisms were determined in 253 Kuwaiti Arab T1DM patients and 214 healthy controls by PCR-RFLP analysis. Serum concentrations of three autoantibodies i.e. ICA (Islet cell autoantibody), GADA (Glutamic acid decarboxylase) and INS (Insulin autoantibody) were determined by radio-immunoassays.ResultsStatistically significant differences were detected between the genotypes of two VDR gene polymorphisms (FokI, C > T, rs10735810 and TaqI, C > T, rs731236) between T1DM patients and controls (P < 0.0001). In both, the frequency of variant alleles was considerably high in T1DM than in the controls. In contrast, the VDR gene ApaI (G > T, rs7975232) and BsmI (A > G, rs1544410) polymorphisms did not show association with T1DM. The homozygous variant genotypes of FokI, ApaI and TaqI polymorphisms show significant differences between various age-of-onset subgroups while no such association was detected in the case of BsmI polymorphism. Significant differences were also noted between heterozygous genotypes of all four polymorphisms especially between 4-6y and > 6y age-of-onset subgroups of T1DM patients. Three autoantibodies, ICA (Islet cell), GADA (glutamate decarboxylase) and INS (insulin) were positively associated to, varying degrees, with T1DM in Kuwaiti Arabs harboring different VDR gene polymorphism genotypes.ConclusionsOur results demonstrate a significant effect of two VDR gene polymorphisms (FokI and TaqI) and three autoantibodies on genetic susceptibility of T1DM in Kuwaiti Arabs along with other factors.

Highlights

The incidence of type 1 diabetes mellitus (T1DM) in Kuwait is amongst the highest in the world
This study investigated an association of four vitamin D receptor (VDR) gene polymorphisms with susceptibility of T1DM in Kuwaiti Arabs by comparing the genotype frequencies between patients and the controls
In contrast to the positive associations with TaqI C-allele from Kuwait and Korea, the results reported from Germany, showed that frequency of TT genotype of VDR gene TaqI polymorphism was higher in T1DM patients than in the controls [54]

Summary

Introduction

The incidence of type 1 diabetes mellitus (T1DM) in Kuwait is amongst the highest in the world. Vitamin D has been shown to exert its effects via a nuclear vitamin D receptor (VDR) and VDR gene may be considered a candidate for T1DM susceptibility. It has been reported that the VDR gene polymorphisms have been associated with altered gene expression or gene function [21] These four VDR gene polymorphisms have been studied in several different populations (including India, Japan, Iran and Finland) for their association with T1DM with inconsistent results [22,23,24,25]. Boraska et al [26] reported an association of VDR gene Tru9I polymorphism and Tru9I-BsmI haplotypes with T1DM in patients from South Croatia. No significant association between three VDR gene polymorphisms (BsmI, ApaI and TaqI) and T1DM was detected in patients from Chile [27]. We determined the serum concentrations of three autoantibodies in Kuwaiti children with T1DM and explored their pattern of association with different VDR gene polymorphism genotypes

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