TY - JOUR
T1 - The X-chromosome has a different pattern of gene expression in women compared with men with ischemic stroke
AU - Stamova, Boryana
AU - Tian, Yingfang
AU - Jickling, Glen
AU - Bushnell, Cheryl
AU - Zhan, Xinhua
AU - Liu, Dazhi
AU - Ander, Bradley P.
AU - Verro, Piero
AU - Patel, Vihar
AU - Pevec, William C.
AU - Hedayati, Nasim
AU - Dawson, David L.
AU - Jauch, Edward C.
AU - Pancioli, Arthur
AU - Broderick, Joseph P.
AU - Sharp, Frank R.
PY - 2012/2
Y1 - 2012/2
N2 - Background and Purpose-: Differences in ischemic stroke between men and women have been mainly attributed to hormonal effects. However, sex differences in immune response to ischemia may exist. We hypothesized that differential expression of X-chromosome genes in blood immune cells contribute to differences between men and women with ischemic stroke. Methods-: RNA levels of 683 X-chromosome genes were measured on Affymetrix U133 Plus2.0 microarrays. Blood samples from patients with ischemic stroke were obtained at ≤3 hours, 5 hours, and 24 hours (n=61; 183 samples) after onset and compared with control subjects without symptomatic vascular diseases (n=109). Sex difference in X-chromosome gene expression was determined using analysis of covariance (false discovery rate ≤0.05, fold change ≥1.2). Results-: At ≤3, 5, and 24 hours after stroke, there were 37, 140, and 61 X-chromosome genes, respectively, that changed in women; and 23, 18, and 31 X-chromosome genes that changed in men. Female-specific genes were associated with post-translational modification, small-molecule biochemistry, and cell-cell signaling. Male-specific genes were associated with cellular movement, development, cell-trafficking, and cell death. Altered sex specific X-chromosome gene expression occurred in 2 genes known to be associated with human stroke, including galactosidase A and IDS, mutations of which result in Fabry disease and Hunter syndrome, respectively. Conclusions-: There are differences in X-chromosome gene expression between men and women with ischemic stroke. Future studies are needed to decipher whether these differences are associated with sexually dimorphic immune response, repair or other mechanisms after stroke, or whether some of them represent risk determinants.
AB - Background and Purpose-: Differences in ischemic stroke between men and women have been mainly attributed to hormonal effects. However, sex differences in immune response to ischemia may exist. We hypothesized that differential expression of X-chromosome genes in blood immune cells contribute to differences between men and women with ischemic stroke. Methods-: RNA levels of 683 X-chromosome genes were measured on Affymetrix U133 Plus2.0 microarrays. Blood samples from patients with ischemic stroke were obtained at ≤3 hours, 5 hours, and 24 hours (n=61; 183 samples) after onset and compared with control subjects without symptomatic vascular diseases (n=109). Sex difference in X-chromosome gene expression was determined using analysis of covariance (false discovery rate ≤0.05, fold change ≥1.2). Results-: At ≤3, 5, and 24 hours after stroke, there were 37, 140, and 61 X-chromosome genes, respectively, that changed in women; and 23, 18, and 31 X-chromosome genes that changed in men. Female-specific genes were associated with post-translational modification, small-molecule biochemistry, and cell-cell signaling. Male-specific genes were associated with cellular movement, development, cell-trafficking, and cell death. Altered sex specific X-chromosome gene expression occurred in 2 genes known to be associated with human stroke, including galactosidase A and IDS, mutations of which result in Fabry disease and Hunter syndrome, respectively. Conclusions-: There are differences in X-chromosome gene expression between men and women with ischemic stroke. Future studies are needed to decipher whether these differences are associated with sexually dimorphic immune response, repair or other mechanisms after stroke, or whether some of them represent risk determinants.
KW - gender
KW - gene expression profiling
KW - ischemic stroke
KW - sex
KW - X-chromosome
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U2 - 10.1161/STROKEAHA.111.629337
DO - 10.1161/STROKEAHA.111.629337
M3 - Article
C2 - 22052522
AN - SCOPUS:84856453910
VL - 43
SP - 326
EP - 334
JO - Stroke
JF - Stroke
SN - 0039-2499
IS - 2
ER -