Abstract
Very few studies have evaluated associations of human leukocyte antigen (HLA) with motor neuron diseases (MND). Using an immunogenetic epidemiological approach, we identified a population-level HLA profile for MND by evaluating the correlations between the population frequencies of 127 HLA Class I and II alleles and the population prevalence of MND in 14 Continental Western European countries. The results demonstrated that significantly more HLA alleles, particularly for Class I, were negatively associated with the population prevalence of MND, suggesting a preponderance of protective vs susceptibility effects. The findings add to the limited literature implicating HLA in MND and considering the role of HLA in immune system responses to pathogens, suggest a potential influence of pathogens in MND.
Highlights
Motor neuron diseases (MND) are a highly disabling group of neurodegenerative diseases characterized by upper and/or lower motor neuron degeneration
The results demonstrated that significantly more human leukocyte antigen (HLA) alleles, for Class I, were negatively associated with the population prevalence of motor neuron diseases (MND), suggesting a preponderance of protective vs susceptibility effects
In light of the largely undetermined genetic influence on Amyotrophic lateral sclerosis (ALS) and other motor neuron diseases and the potential etiological involvement of microorganisms, we focused here on the immunogenetic influence of human leukocyte antigen (HLA), a region of genes on chromosome 6 that are involved in immune response to foreign antigens
Summary
Motor neuron diseases (MND) are a highly disabling group of neurodegenerative diseases characterized by upper and/or lower motor neuron degeneration. Neuropathological features include loss of motor neurons as well as cytoplasmic inclusions that mirror those seen in frontotemporal dementia[2]. As ALS progresses, cognitive symptoms often emerge with varying degrees of impairment up to and including dementia, commonly of the frontotemporal type[3,4]. The course, phenotype, and survival time of ALS have been shown to vary geographically in relation to population ancestral origin, pointing towards a modulatory influence of genetic and environmental factors that vary by population[5]. A number of genes have been implicated in ALS, many of which overlap with frontotemporal dementia[6,7,8]. Several risk factors including smoking, physical activity, environmental and occupational exposures, head injuries, and diet have been investigated with varying degrees of support[9,10]. With the exception of spinal muscular atrophy and hereditary spastic
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