Abstract
Multiple Sclerosis (MS) is a complex chronic neurodegenerative disorder resulting from an autoimmune reaction against myelin. So far, many genetic variants have been reported to associate with MS risk however their association is inconsistent across different populations. Here we investigated the association of the most consistently reported genetic MS risk variants in the Kuwaiti MS population in a case-control study designs. Of the 94 reported MS risk variants four variants showed MS risk association in Arabs exome analysis (EVI5 rs11808092 p = 0.0002; TNFRSF1A rs1800693 p = 0.00003; MTHFR rs1801131 p = 0.038; and CD58 rs1414273 p = 0.00007). Replication analysis in Kuwaiti MS cases and healthy controls confirmed EVI5 rs11808092A (OR: 1.6, 95%CI: 1.19–2.16, p = 0.002) and MTHFR rs1801131G (OR: 1.79, 95%CI: 1.3–2.36, p = 0.001) as MS risk genetic factors, while TNFRSF1A rs1800693C had a marginal MS risk association (OR: 1.36, 95%CI: 1.04–1.78, p = 0.025) in the Kuwaiti population. CD58 rs1414273 did not sustain risk association (p = 0.37). In conclusion, EVI5 rs11808092A, TNFRSF1A rs1800693C and MTHFR rs1801131G are MS risk factors in the Kuwaiti population. Further investigations into their roles in MS pathogenesis and progression are merited.
Highlights
Multiple Sclerosis (MS) is a complex, chronic, neurodegenerative autoimmune disorder that affects the central nervous system (CNS)
The most significant associations were seen with polymorphisms in human leukocyte antigen (HLA) HLA-DR2 alleles, their association was found variable across different MS populations[9,10]
Genotype frequencies were significantly different among the two cohorts for only three variants; TNFRSF1A rs1800693 (p = 0.0001), Methylenetetrahydrofolate Reductase (MTHFR) rs1801131 (p = 0.024), and CD58 rs1414273 (p = 0.0001)
Summary
Multiple Sclerosis (MS) is a complex, chronic, neurodegenerative autoimmune disorder that affects the central nervous system (CNS). The lesions represent an endpoint of repeated autoimmune attacks against endogenous myelin-associated antigens which lead to neuroaxonal degeneration, and death of myelin forming cells; the oligodendrocytes. This pathological process results in demyelinated plaques or astrocytic scars throughout the CNS perturbing neural networks[1]. Environmental and genetic contributing factors to MS incidence are not exclusive but are thought to be synergistic as none of these factors fully explain causation alone, nor do they consistently associate with MS risk across different populations[7]. To confirm the association of reported MS risk genetic factors, replication studies should be conducted across different MS populations to understand the influence of ethnic and geo-epidemiological factors on MS risk. Our objective was to assess their association in a semi-ethnically homogeneous Kuwaiti cohort as these genetic risk factors were identified from multi-ethnic MS populations
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