Department of Human Genetics, University of Chicago, Chicago, IL, 60637, USA.
Sci Rep. 2021 Jan 13;11(1):1107. doi: 10.1038/s41598-020-80145-z.
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.
许多常见的复杂疾病，尤其是免疫介导性疾病，其患病率存在明显的性别差异，这一点已有充分的文献记载。然而，与生物学性别相关的因素在整个生命周期中发挥作用的确切机制尚不清楚。我们调查了 46 名男性和 66 名女性哈特派社区成员的外周血白细胞（PBL）对脂多糖（LPS）的先天免疫刺激的性别特异性转录反应，哈特派社区实行集体生活。我们鉴定出了 1217 个常染色体和 54 个 X 连锁基因，这些基因对 LPS 有性别特异性反应，以及 71 个常染色体和一个 X 连锁性别特异性表达数量性状基因座（eQTL）。尽管与所有表达的常染色体基因相比，HLA 基因中对 LPS 有反应的基因比例相似，但在 HLA 基因中，存在与处理相互作用的基因的性别显著过表达。我们还观察到，与常染色体基因相比，X 连锁基因中 LPS 反应的性别特异性差异表达基因富集，这表明 HLA 和 X 连锁基因可能不成比例地导致免疫介导性疾病风险的性别差异。
