Assessment of vitamin D-binding protein (DBP) gene polymorphisms and their correlation with multiple sclerosis: a case-control study in a sample of the Syrian population

Bushra Alhomsi,Imad Alkadi,Ghalia Aboualchamat

doi:10.1186/s43042-020-00076-2

Bushra Alhomsi, Imad Alkadi + Show 1 more

Open Access

https://doi.org/10.1186/s43042-020-00076-2

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Abstract

BackgroundVitamin D deficiency is a major health concern as it increases the risk of developing many serious diseases. Recently, the correlation between vitamin D deficiency and multiple sclerosis (MS) is a matter of serious debate. In this case-control study, we aimed to assess the correlation between genetic changes in the vitamin D-binding protein (DBP) gene and their consequence on MS patients. Our sample study consisted of 110 individuals; 40 patients with MS as cases and 70 healthy controls. Vitamin D levels were determined by immunofluorescence assay, and polymorphisms at rs7041 (c.1296 T > G p.Asp416Glu) and rs4588 (c.1307C > A p.Thr420Lys) of the DBP gene were genotyped using PCR/RFLP method for all cases and controls.ResultsOur results showed that genotype frequencies were consistent with Hardy-Weinberg equilibrium. A significant association was found in rs7041 (c.1296TT) homozygous wild-type, and the odds ratio was < 1 suggesting a protective role against developing MS (OR; 0.03, p = 0.0002) whereas the c.1296GG genotype was significantly correlated with an increased risk for MS by 6 folds (OR: 6.0000, p < 0.0001). No significant association was noted at rs4588 and MS occurrence. In addition, our compound genotyping results revealed that haplotypes 1S-1S are 6 times more likely to develop MS, whereas haplotypes 1F-1F had a more protective role in MS patients (OR: 0.063, p = 0.06.), respectively. The risk of vitamin D insufficiency in patients was greater by 14 folds compared to controls (OR: 14.05, p = 0.0128). Furthermore, the c.1296GG genotype was associated significantly by more than 4 times with insufficient levels of vitamin D and by 7 folds with vitamin deficiency.ConclusionsWe conclude that polymorphisms in the DBP gene could have independent effects on the risk of developing multiple sclerosis. The homozygous recessive genotype at rs7041 was associated with insufficient levels of vitamin D and with the risk of MS emergence.

Highlights

Vitamin D deficiency is a major health concern as it increases the risk of developing many serious diseases
Our sample study consisted of 110 individuals; 40 patients with multiple sclerosis and 70 healthy controls
Our data showed that the wild type CC was frequently detected amongst patients and controls (75% and 62.9%, respectively), and the homozygous genotype AA was rare in controls and was not detected at all amongst multiple sclerosis (MS) patients (Table 1)

Summary

Introduction

Vitamin D deficiency is a major health concern as it increases the risk of developing many serious diseases. The correlation between vitamin D deficiency and multiple sclerosis (MS) is a matter of serious debate In this case-control study, we aimed to assess the correlation between genetic changes in the vitamin Dbinding protein (DBP) gene and their consequence on MS patients. It is well known that the DBP gene has many polymorphic regions amongst humans [10, 11] Genetic variants in this gene affect the transfer of vitamin D in the body, leading to its deficiency [12]. Several studies argued the effect of genetic changes in the DBP gene and the risk of developing multiple sclerosis (MS) [16,17,18]. We aimed in this study to investigate whether the common genetic variants rs7041 and rs4588 in the DBP gene have an influence on MS development and vitamin D levels in a sample of Syrian population

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