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

Abstract

Background: 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. 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. Results: Frequency 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. Conclusion: The 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.

Association of vitamin D receptor gene polymorphisms with type 2 diabetes mellitus in Taif population: a case-control study

“…In a study conducted two years ago, researchers have reported that VDR polymorphisms were associated with arthritis development in a Pakistani society (Mukhtar et al, 2019). Another study has suggested that VDR polymorphisms have a protective link against Multiple sclerosis in Egyptian society (Hassab et al, 2019). In addition, Barbara Angel and her colleagues reported that VDR polymorphisms are associated with type 2 diabetes in older individuals among the Santiago de Chile population (Angel et al, 2018).…”

Vitamin D receptor gene polymorphism in Egyptian multiple sclerosis patients

“…On the contrary, the study of Tajouri et al, 2005 23 detected a predominance for the A allele in MS, although the genotype distribution was not significantly different between patients and controls. Similarly, Hassab et al, 2019 26 found a significant association of A allele with MS risk (OR= 2.47, p= 0.008). The meta-analysis by Tizaoui et al, 2015 27 suggested that the homozygote wild AA genotype was a significant MS risk factor.…”

“…However, our findings are inconsistent with the results of other studies that showed an association between VDR FokI polymorphisms and MS pathogenesis. An Egyptian study by Hassab et al, 2019 26 found a statistically significant higher percentage of FokI genotypes (AG+GG) in the healthy controls compared to MS cases with a statistically significant association of the "G" allele in the control group, indicating the possibility that the "G" allele is associated with lower MS risk (OR= 0.42, p= 0.015). The meta-analysis of 13 casecontrol studies by Tizaoui et al, 2015 27 reported an association of the wild AA genotype of FokI with an increased susceptibility of MS in a total of 3300 MS patients and 3194 healthy control subjects.…”

Association of Vitamin-D Receptor Gene Single Nucleotide Polymorphism (FokI) with COPD

“…Therefore, this FokI polymorphism may affect the activity of VDR and subsequent downstream effects of vitamin D 53 , including its immunomodulatoryrole 50,51 . FokI VDR SNP was found to be associated with essential hypertension, metabolic syndrome, acromegaly, leprosy, hepatocellular carcinoma, multiple sclerosis, urolithiasis and skeletal muscle strength in COPD patients 13,22,23,29,35,44,47,54 . From the perspective of respiratory ailments, FokI VDR SNP was found to be associated with asthma and tuberculosis 39,41,42 .…”