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Sunday

 

MS, Systemic Lupus Linked by Genetic Variant























Image Source: KENTUCKYFERTILITY

HealthDay News -- A genetic variant that is associated with both multiple sclerosis and systemic lupus erythematosus (SLE) has been identified, according to a study published in the New England Journal of Medicine.

Maristella Steri, PhD, from Istituto di Ricerca Genetica e Biomedica in Italy, and colleagues conducted a genome-wide association study in multiple sclerosis as well as TNFSF13B locus-specific association testing in SLE. To identify the causal variant and determine its mechanism of action, they performed extensive phenotyping of quantitative immune variables, sequence-based fine mapping, cross-population and cross-phenotype analyses, and gene expression studies.
 
The researchers found that a variant in TNFSF13B, encoding the cytokine and drug target B-cell activating factor (BAFF), was associated with both multiple sclerosis and SLE. There was also an association between the disease-risk allele and up-regulated humoral immunity through increased levels of soluble BAFF, B lymphocytes, and immunoglobulins. An insertion-deletion variant, GCTGT→A (in which A is the risk allele) was identified as the causal variant and yielded a shorter transcript that escaped microRNA inhibition and increased production of soluble BAFF. This in turn up-regulated humoral immunity. This autoimmunity variant has been evolutionarily advantageous, based on population genetic signatures, most likely by augmenting resistance to malaria.

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