Native ancestry is associated with optic neuritis and age of onset in hispanics with multiple sclerosis

Abstract

Background and ObjectiveHispanics with multiple sclerosis (MS) present younger and more often with optic neuritis (ON) as compared to Whites in the western United States. Regional differences related to Hispanic genetic admixture could be responsible. We investigated the association between global genetic ancestry and ON and age at onset of MS in Hispanics.MethodsData were obtained for 1033 self‐identified Hispanics with MS from four MS‐based registries from four academic institutions across the United States January 2016–April 2017. Multivariate regression models, utilizing genetic ancestry estimates for Native American (NA), African, and European ancestry, were used to assess the relationship between genetic ancestry and ON presentation and age of MS onset, defined as age at first symptom.ResultsGenetic ancestry and ON proportions varied by region where NA ancestry and ON proportions were highest among Hispanics in the southwestern United States (40% vs. 19% overall for NA and 38% vs. 25% overall for ON). A strong inverse correlation was observed between NA and European ancestry (r = −0.83). ON presentation was associated with younger age of onset (OR: 0.98; 95% CI: 0.96–0.99; P = 7.80 × 10−03) and increased NA ancestry (OR: 2.35 for the highest versus the lowest quartile of NA ancestry; 95% CI: 1.35–4.10; P = 2.60 × 10−03). Younger age of onset was found to be associated with a higher proportion NA (Beta: −5.58; P = 3.49 × 10−02) and African ancestry (Beta: −10.07; P = 1.39 × 10−03).InterpretationEthnic differences associated with genetic admixture could influence clinical presentation in Hispanics with MS; underscoring the importance of considering genetic substructure in future clinical, genetic, and epigenetic studies in Hispanics.

Race and ethnicity on MS presentation and disease course

“…On average, our own work in Hispanics with MS further highlights the genetic ancestral differences between Hispanic groups; Mexican-Americans have a higher proportion of Native American ancestry (~38%) but lower African ancestry (average 7%) than Puerto Ricans who have on average 15% or higher African ancestry ( Figure 1). (10,11) Summary: Race and ethnicity, combined, is a multidimensional construct that reflects exposure to external health risks posed by environmental, genetic, social, and behavioral factors. Examining the ancestral heterogeneity in Hispanics and African Americans, could help detect genetic variation which can be used as a tool to sort biological from nonbiological explanations of MS.(9)…”

“…Both an increase in African (beta=−10.07, P=1.39×10 −03 ) and Native American (beta= −5.58, P=3.49 × 10 −02 ) ancestry contributed to a younger age at first symptom. (11) Summary: Geographical location before onset of multiple sclerosis remains a risk factor in MS and studies of both African and Native American genetic ancestry demonstrate an increased risk for younger age of onset. While our data lend support to this hypothesis, we recognize the need for more complete environmental studies that integrate genetic ancestry and migration details.…”

Matrine protects retinal ganglion cells from apoptosis in experimental optic neuritis

“…In 15%-20% of individuals who eventually develop MS, ON is their rst sign of disease. An acute, self-limited episode of optic nerve in ammation results in demyelination, accompanied by temporary or permanent loss of vision (6,7).…”

Matrine protects retinal ganglion cells from apoptosis in experimental optic neuritis

“…In 15%-20% of individuals who eventually develop MS, ON is their first sign of disease. An acute, self-limited episode of optic nerve inflammation results in demyelination, accompanied by temporary or permanent loss of vision (6,7).…”