Y Chromosome Gene Expression in the Blood of Male Patients With Ischemic Stroke Compared With Male Controls

Abstract

Background and Purpose Gender is suggested to be an important determinant of ischemic stroke risk factors, etiology and outcome. However, the basis for this remains unclear. The Y chromosome is unique in males. Genes expressed in men on the Y chromosome that are associated with stroke may be important genetic contributors to the unique features of males with ischemic stroke, which would be helpful for explaining sex differences observed between men and women. Methods Blood samples were obtained from 40 males at ≤ 3, 5 and 24 hours following ischemic stroke and from 41 male controls (July 2003- April 2007). RNA was isolated from blood and processed on Affymetrix Human U133 Plus 2.0 Arrays. Y chromosome genes differentially expressed between male stroke and male control subjects were identified using an analysis of covariance (ANCOVA) adjusted for age and batch. A p<0.05 and fold change (FC) > ∣1.2∣ were considered significant. Results Seven genes on the Y chromosome were differentially expressed in males with ischemic strokes compared to controls. Five of these genes (VAMP7, CSF2RA, SPRY3, DHRSX, PLCXD1,) are located on pseudoautosomal regions (PARs) of the human Y chromosome. The other two genes (EIF1AY and DDX3Y) are located on the non-recombining region of the human Y chromosome (NRY). The identified genes were associated with immunology, RNA metabolism, vesicle fusion and angiogenesis. Conclusions Specific genes on the Y chromosome are differentially expressed in blood following ischemic stroke. These genes provide insight into potential molecular contributors to sex differences in ischemic stroke.

The Klinefelter syndrome is associated with high recurrence of copy number variations on the X chromosome with a potential role in the clinical phenotype

“…It is located in PAR1 of both sex chromosomes and its increased expression in KS has been associated with insulin resistance, waist circumference, and concentrations of the procoagulatory substance PAI‐1 and cytokines (Zitzmann et al ., ). Interestingly, expression of CSF2RA has been also associated with a higher incidence of stroke in men vs. women (Tian et al ., ), probably related to its angiogenic properties (Buschmann et al ., ). KS subjects have an increased risk of cardiovascular diseases, in particular for pulmonary embolism, cerebrovascular disease, peripheral vascular disease, subarachnoid hemorrhage (Priddle & Crow, ), left ventricular diastolic dysfunction, impaired cardiopulmonary performance, chronotropic incompetence, and increased intima‐media thickness (Swerdlow et al ., ) and reduced artery diameters (Foresta et al ., ).…”

The Effects of Estrogen in Ischemic Stroke

“…Differential expression by sex of autosomal [72] and X-chromosome genes [73] have been identified in blood samples of ischemic stroke patients, and differential expression of Y-chromosome genes have been identified in male stroke patients compared with male controls [74]. Animal models have recently been developed that may help dissect out the effects of chromosomal sex and hormone exposure including the “Four Core Genotype” and the “Y consomic rat” model, but each has limitations (see reviews [75, 76]).…”

The cis and trans effects of the risk variants of coronary artery disease in the Chr9p21 region

“…CASP14 plays a central role in the execution phase of cell apoptosis and is overexpressed in tumors [ 58 ]. EIF1AY is on the Y chromosome and is overexpressed in men who have experienced a stroke [ 59 ]. DUT encodes an essential enzyme of nucleotide metabolism, which is vital to DNA replication [ 60 ].…”