Analysis of Single Nucleotide Polymorphisms in HLA-DRA, IL2RA , and HMGB1 Genes in Multiple Sclerosis.

Azam Moslemi,Rozita Doosti,Fereidoun Mahboudi,Morteza Karimpoor,Hamid Alinejad Rokni,Mohammad Ali Sahraian,Maryam Lotfi,Nima Motamed,Hamzeh Rahimi,Mohsen Asouri,Sadegh Fattahi,Haleh Akhavan‐Niaki

doi:10.29252/rbmb.9.2.199

Abstract

Multiple sclerosis (MS) is a common demyelinating neurodegenerative disorder with significant heritability. Previous studies have associated genetic variants in human leukocyte antigen (HLA) complex, IL2RA , and HMGB1 genes with the pathophysiology of MS. In order to investigate the gene association in the Iranian population, we performed a genotyping study of 36 variants in the mentioned genes using Sanger sequencing in 102 MS patients and 113 healthy controls. Our results identified significant associations as well as significant allele frequency differences in some of the studied single-nucleotide polymorphisms including rs4935356, rs3177928, and rs7197 from HLA-DRA gene, and rs12722489 and rs12722490 variants from IL2RA gene (p< 0.05). Moreover, the strong linkage disequilibrium of two common haplotypes was estimated from the HLA-DRA gene. This association study may suggest the role of these polymorphisms in the genetic susceptibility of MS in the Iranian population and would facilitate the recognition of causative variants in this disease.

Highlights

Multiple sclerosis (MS) is the most common autoimmune neurologic disease which affects approximately two million new cases worldwide, especially young adults [1]
Upon analysis of the polymorphisms of HMGB1 gene, the genotype and allele frequencies of rs146076135, rs201945336, rs111892138, rs200308321, rs149637108, rs538493533, rs577524260, and rs182881863 SNPs were calculated and, no significant difference was observed in allele and genotype frequencies in both groups (p> 0.05) (Table 5)
Meta-analysis studies suggest that human leukocyte antigen (HLA)-DR2, and the DRB1*15 allele, are significant risk determinants in Chinese MS patients, less strong correlations were revealed in Western MS populations; whereas, HLA-DR9 alleles appeared to confer the resistance to disease in this population [13]

Summary

Introduction

Multiple sclerosis (MS) is the most common autoimmune neurologic disease which affects approximately two million new cases worldwide, especially young adults [1]. The immunological studies have shown that dis- Both environmental and genetic factors are involved in the etiology of MS. Genetic factors are primarily responsible for the increased frequency of the disease in the relatives of affected individuals. Previous studies have associated genetic variants in human leukocyte antigen (HLA) complex, IL2RA, and HMGB1 genes with the pathophysiology of MS. Results: Our results identified significant associations as well as significant allele frequency differences in some of the studied single-nucleotide polymorphisms including rs4935356, rs3177928, and rs7197 from HLA-DRA gene, and rs12722489 and rs12722490 variants from IL2RA gene (p< 0.05). Conclusions: This association study may suggest the role of these polymorphisms in the genetic susceptibility of MS in the Iranian population and would facilitate the recognition of causative variants in this disease

Objectives

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Results

Conclusion