Novel targeted therapies for African-American and European-American SLE patients identified from E-Genes elucidated by transancestral SNP mapping

SLE is more prevalent and severe in African-American (AA) compared with European-American (EA) populations but standard-of-care drugs vary in effectiveness between these groups. To gain insight, drugs specific for E-gene containing pathways were investigated using the Immunochip transancestral SNP m...

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Bibliographic Details
Published in:	The Journal of immunology (1950) Vol. 200; no. 1_Supplement; pp. 175 - 175.21
Main Authors:	Aidukaitis, Bryce N., Labonte, Adam C., Catalina, Michelle D., Bachali, Prathyusha, Rouffa, Sean, Ainsworth, Hannah C., Marion, Miranda C., Howard, Timothy D., Langefeld, Carl D., Lipsky, Peter E., Grammer, Amrie C.
Format:	Journal Article
Language:	English
Published:	01-05-2018
Online Access:	Get full text
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Summary:	SLE is more prevalent and severe in African-American (AA) compared with European-American (EA) populations but standard-of-care drugs vary in effectiveness between these groups. To gain insight, drugs specific for E-gene containing pathways were investigated using the Immunochip transancestral SNP mapping and a curated database of SLE DE genes. SNPs proxy to SLE-associated SNPs were compared with known eQTLs contained in the GTEx database. Since GTEx contains genotype data as well as gene expression data from cell lines, tissues and whole blood from healthy individuals, an independent query of GTEx for expression of RNAs abnormally expressed in SLE patients compared to healthy individuals was carried out. The results of the eQTL and DE gene queries of GTEx were combined and eQTLs and associated E-Genes were pooled by ancestry. Drugs targeting E-genes/pathways shared by EA and AA include ibrutinib, ruxolitinib and ustekinumab. Predicted EA-specific drugs include antimalarials and cyclosporine, as well as drugs-in-development targeting CD40, CXCR1 and CXCR2; AA-specific drugs include retinoids and HDAC inhibitors. This analysis of the distinct genetic profiles of EA and AA populations indicates that unique sets of drugs may be particularly effective at treating lupus in each ancestral group.
ISSN:	0022-1767 1550-6606
DOI:	10.4049/jimmunol.200.Supp.175.21