Protective association of VDR gene polymorphisms and haplotypes with multiple sclerosis patients in Egyptian population

Amina H Hassab,Amira I Fayad,Ireny M Tawadros,Dalia A Elneely,Ahmed H Deif

doi:10.1186/s43042-019-0009-2

Amina H Hassab, Amira I Fayad + Show 3 more

Open Access

https://doi.org/10.1186/s43042-019-0009-2

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Abstract

BackgroundHypovitaminosis D is one of the hazardous factors for multiple sclerosis (MS) and can be attested by expanding clinical studies. We aimed to study vitamin D receptor (VDR) gene polymorphisms: FokI, BsmI, ApaI, TaqI, and Tru9I genotype; frequency; haplotype structure; and linkage disequilibrium (LD) in MS Egyptian patients. The study was conducted on 50 MS patients and 50 healthy controls of matching age and sex. Alleles and genotype variants of VDR gene SNPs were analyzed by PCR using the restriction fragment length polymorphism (RFLP). Haplotype and linkage disequilibrium analysis based on the five genetic loci was studied on the detected genotypes.ResultsFrequency of FokI genotype (Ff+ff) was significantly higher in healthy controls (50%) compared to MS (28%) (P = 0.03), and “f” allele was significantly associated with the control group (OR = 0.42, CI = 0.26–0.85, P = 0.015). Frequency of ApaI genotype (Aa+aa) was significantly higher in MS (60%) (P = 0.002), and “a” allele was significantly associated with MS cases (OR = 2.47, CI = 1.25–4.88, P = 0.008). TaqI allelic distribution showed significant association of “t” allele with control group (OR = 0.55, CI = 0.31–0.98, P = 0.04). Statistically significant LD was detected between BsmI and ApaI in controls and MS (D' = 0.89 and P < 0.001, and D' = 0.52 and P < 0.001), respectively. Odd ratios of “fAt” and “BAt” were 0.2 (95% CI = 0.06–0.66) and 0.43 (95% CI = 0.19–0.97), respectively, suggesting that MS risk was 5 times and 2.3 times lesser, respectively, for haplotype carriers compared to non-carriers.ConclusionThe study findings suggest that VDR gene variants “f,” “A,” and “t” alleles as well as VDR gene haplotypes “BAt” and “fAt” may have a protective effect against MS disease in Egyptian population.

Highlights

Hypovitaminosis D is one of the hazardous factors for multiple sclerosis (MS) and can be attested by expanding clinical studies
Subjects One hundred subjects were recruited in this study and divided into 2 groups: group I, 50 MS patients that were diagnosed according to McDonald criteria [23], and group II, 50 healthy subjects of matching age and sex were included as a control group
Studied MS patients were categorized according to clinical and neurological examination into relapsing/remitting MS (RRMS) which is characterized by clearly discrete attacks with neurological stability between attacks (n = 44 (88%)) and secondary progressive MS (SPMS) which usually starts as RRMS with progressive worsening of neurologic function (n = 6 (12%)), while primary progressive MS (PPMS) which is characterized by deteriorating neurologic function from the onset of symptoms without acute attacks or progressive relapsing MS (PRMS) which is characterized by steady functional deterioration with occasional attacks had no presentation among studied MS cases

Summary

Introduction

Hypovitaminosis D is one of the hazardous factors for multiple sclerosis (MS) and can be attested by expanding clinical studies. We aimed to study vitamin D receptor (VDR) gene polymorphisms: FokI, BsmI, ApaI, TaqI, and Tru9I genotype; frequency; haplotype structure; and linkage disequilibrium (LD) in MS Egyptian patients. Alleles and genotype variants of VDR gene SNPs were analyzed by PCR using the restriction fragment length polymorphism (RFLP). Multiple sclerosis (MS) is an immunoinflammatory and neurodegenerative disease caused by autoimmune reaction to the central nervous system (CNS) [1]. These inflammatory insults result in MS symptoms such as optic nerve damage and motor difficulty [2]. Our aim was to study the genotype and frequency of VDR gene polymorphisms: FokI, BsmI, ApaI, TaqI, and Tru9I, in MS Egyptian patients. No previous studies have covered those genetic aspects in MS Egyptian population, and we believe it may help in establishing clinical registries for future studies

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