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Sex-specific differences in peripheral blood leukocyte transcriptional response to LPS are enriched for HLA region and X chromosome genes.


ABSTRACT: Sex-specific differences in prevalence are well documented for many common, complex diseases, especially for immune-mediated diseases, yet the precise mechanisms through which factors associated with biological sex exert their effects throughout life are not well understood. We interrogated sex-specific transcriptional responses of peripheral blood leukocytes (PBLs) to innate immune stimulation by lipopolysaccharide (LPS) in 46 male and 66 female members of the Hutterite community, who practice a communal lifestyle. We identified 1217 autosomal and 54 X-linked genes with sex-specific responses to LPS, as well as 71 autosomal and one X-linked sex-specific expression quantitative trait loci (eQTLs). Despite a similar proportion of the 15 HLA genes responding to LPS compared to all expressed autosomal genes, there was a significant over-representation of genes with sex by treatment interactions among HLA genes. We also observed an enrichment of sex-specific differentially expressed genes in response to LPS for X-linked genes compared to autosomal genes, suggesting that HLA and X-linked genes may disproportionately contribute to sex disparities in risk for immune-mediated diseases.

SUBMITTER: Stein MM 

PROVIDER: S-EPMC7806814 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Sex-specific differences in peripheral blood leukocyte transcriptional response to LPS are enriched for HLA region and X chromosome genes.

Stein Michelle M MM   Conery Mitch M   Magnaye Kevin M KM   Clay Selene M SM   Billstrand Christine C   Nicolae Raluca R   Naughton Katherine K   Ober Carole C   Thompson Emma E EE  

Scientific reports 20210113 1


Sex-specific differences in prevalence are well documented for many common, complex diseases, especially for immune-mediated diseases, yet the precise mechanisms through which factors associated with biological sex exert their effects throughout life are not well understood. We interrogated sex-specific transcriptional responses of peripheral blood leukocytes (PBLs) to innate immune stimulation by lipopolysaccharide (LPS) in 46 male and 66 female members of the Hutterite community, who practice  ...[more]

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