mRNA Expression of GWAS-identified Genes in Peripheral Blood Leukocytes
as Identification Biomarkers for Haemorrhagic Stroke
Abstract
Haemorrhagic stroke (HS) is a devastating form of stroke with a high
fatality rate. The lack of rapid lesion detection limits early diagnosis
of HS. Several susceptibility genes of HS found in genome-wide
association studies (GWAS) warrant transcriptional-level biomarkers for
useful utility. 13 GWAS level loci with minor allele frequency ≥ 0.05
were selected out of 95 loci related to HS. After validation, the mRNA
expression in peripheral leukocytes of 11 genes (PMF1, SLC25A44,
CASZ1, NINJ2, WNK1, DYRK1A, LRCH1, LDLR, SMARCA4, AQP9, and
LIPC) were measured in the HS case-control study (64 HS cases vs.
128 controls), and then verified in an ischemic stroke (IS) case-control
study (67 IS cases vs. 61 controls). LIPC (P=0.002) and
CASZ1 (P=0.040) were downregulated in HS patients, while
SLC25A44 was upregulated (P=0.009). In the IS case-control
study, the differential expression of LIPC (P=0.034) and
SLC25A44 (P<0.001) was observed. Although
CASZ1 expression was not different between IS cases and controls
(P=0.419) with fold change (FC) of 1.205, the direction of
expression was opposite to that in HS case-control study (FC=0.747). The
ROCtrfgs of traditional risk factors and gene score which was estimated
by combining LIPC, CASZ1, and SLC25A44 expression weights,
improved the utility for HS identification by 14.1% compared with
ROCtrf (P=0.001). Expression of LIPC,
CASZ1, and SLC25A44 could serve as potential biomarkers for
identifying HS. CASZ1 might be a cause-specific indicator for
differentiating HS from IS. Transcriptional score of these three genes
could improve performance of the traditional risk model for HS
identification.