Polymorphisms in Interleukin-2 and Interleukin-7 Receptor α-Chain Genes and Human Herpes Virus-6 as Risk Factors for Multiple Sclerosis
Layal Fayad
Department of Experimental Pathology, Immunology and Microbiology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
Aline Kherlopian
Department of Neurology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
Alexander M. Abdelnoor *
Department of Experimental Pathology, Immunology and Microbiology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
Bassem Yamout
Department of Neurology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
Elias A. Rahal
Department of Experimental Pathology, Immunology and Microbiology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
*Author to whom correspondence should be addressed.
Abstract
Aim: The aim of this study was to examine whether a Human herpes virus-6 (HHV-6) infection increases the risk of MS in individuals harboring particular cytokine receptor α-chain gene alleles.
Study Design: MS patients and controls were assessed for HHV-6 DNA and for single nucleotide polymorphisms (SNPs) in their IL7RA and IL2RA genes.
Place and Duration of Study: The study was carried out at the Department of Experimental Pathology, Microbiology and Immunology, American University of Beirut, between March 2011 and March 2013.
Methodology: Blood samples from 100 MS patients and 100 controls were investigated for the presence of HHV-6 by nested PCR. Single nucleotide polymorphisms (SNPs) in the IL7RA and IL2RA genes were examined by restriction fragment length polymorphism.
Results: HHV-6 was detected in 58% of MS patients and 32% of controls (OR = 2.935, 95% CI = 1.582-5.463, p=0.000). We did not detect a statistically significant correlation between MS and the studied rs2104286, rs12722489 SNPs in the IL2RA gene and rs6897932 SNP in the IL7RA gene. Concomitant presence of rs2104286 and HHV-6 was detected in 56% of patients and 30% of controls (OR=2.970, 95% CI=1.594-5.53, P=0.000). Similarly, rs6897932 and HHV-6 were observed in 57% of patients and 28% of controls (OR=3.409, 95% CI= 1.815-6.428, P=0.000). Therefore, double positivity moderately increased the risk of MS compared to either factor alone. HHV-6 and rs12722489 double positivity did not increase the risk of MS.
Conclusion: HHV-6 infections may enhance the risk of MS in subjects with particular genetic determinants.
Keywords: Human herpes virus-6, interleukin 7 receptor α-chain (IL7RA) gene, interleukin 2 receptor α-chain (IL2RA) gene, rs2104286, rs12722489, rs6897932.