P051 - Vitamin D receptor polymorphisms and HLA-class II genotypes among Lebanese with multiple sclerosis – A pilot study

Abstract

Background Multiple sclerosis (MS) is an autoimmune disease with multifactorial etiology. Previous studies showed that HLA-DRB115 allele is a major genetic risk factor for MS in other populations possibly through regulation of vitamin D receptor (VDR) complex. In this study, we investigated the HLA class II genotypes and VDR gene polymorphism among a group of Lebanese MS patients and controls. Methods Fifty MS patients (remitting/relapsing, aged: 19–74years, male:female=1:2.1) were selected for this study, based on the Expanded Disability Status Scale. The controls included: 49 healthy subjects (aged: 15–59years, male:female=1:2) and 51 neurologic patients other than MS (Non-MS, aged 13–70 years, male:female=1:1.12). After a thorough history, blood in EDTA tube was collected. Extracted genomic DNA was used for molecular analysis of VDR genotypes(ApaI, TaqI and BsmI) and HLA class II typing (low resolution HLA-DRB1/3/4/5) (Luminex, San Diego, CA). Differences between groups were evaluated using Mann Whitney-U test. Chi-square test was used for association between various categorical variables (p=0.05); therefore both were combined into one control group for analysis. Frequency of HLA-DRB115 was significantly higher in MS patients compared to controls. None of the VDR gene alleles differed between the two groups. Odds ratio (OR) for MS in the presence of DRB115 allele was 3.21 (p=0.016; 95% CI=1.20–8.59). Cosegregation of HLA-DRB115 and VDR genotypes showed no increase in risk for MS in the presence of A-allele (OR=3.40; p=0.022; 95% CI=1.14–10.19). Similarly, combination of DRB115 with b-allele resulted in higher OR of 4.22 although not statistically significant (p=0.08; 95% CI=0.75–23.89). Conclusion Our results confirm that HLA-DRB115 is a strong predisposing factor for MS in Lebanese patients. Furthermore, the interaction between specific VDR alleles and HLA polymorphism does not significantly increase the susceptibility to MS. Multiple sclerosis (MS) is an autoimmune disease with multifactorial etiology. Previous studies showed that HLA-DRB115 allele is a major genetic risk factor for MS in other populations possibly through regulation of vitamin D receptor (VDR) complex. In this study, we investigated the HLA class II genotypes and VDR gene polymorphism among a group of Lebanese MS patients and controls. Fifty MS patients (remitting/relapsing, aged: 19–74years, male:female=1:2.1) were selected for this study, based on the Expanded Disability Status Scale. The controls included: 49 healthy subjects (aged: 15–59years, male:female=1:2) and 51 neurologic patients other than MS (Non-MS, aged 13–70 years, male:female=1:1.12). After a thorough history, blood in EDTA tube was collected. Extracted genomic DNA was used for molecular analysis of VDR genotypes(ApaI, TaqI and BsmI) and HLA class II typing (low resolution HLA-DRB1/3/4/5) (Luminex, San Diego, CA). Differences between groups were evaluated using Mann Whitney-U test. Chi-square test was used for association between various categorical variables (p=0.05); therefore both were combined into one control group for analysis. Frequency of HLA-DRB115 was significantly higher in MS patients compared to controls. None of the VDR gene alleles differed between the two groups. Odds ratio (OR) for MS in the presence of DRB115 allele was 3.21 (p=0.016; 95% CI=1.20–8.59). Cosegregation of HLA-DRB115 and VDR genotypes showed no increase in risk for MS in the presence of A-allele (OR=3.40; p=0.022; 95% CI=1.14–10.19). Similarly, combination of DRB115 with b-allele resulted in higher OR of 4.22 although not statistically significant (p=0.08; 95% CI=0.75–23.89). Our results confirm that HLA-DRB115 is a strong predisposing factor for MS in Lebanese patients. Furthermore, the interaction between specific VDR alleles and HLA polymorphism does not significantly increase the susceptibility to MS.