Carriers of the coronary artery disease-predisposing haplogroup I of the Y chromosome had 0.61- and 0.64-fold lower expression of UTY and PRKY genes in macrophages (P=0.0001 and P=0.002).
Meta-Analysis (n=1,988)
Yes
Is haplogroup I of the Y chromosome associated with traditional cardiovascular risk factors or altered macrophage gene expression in European men?
The increased coronary artery disease risk associated with Y chromosome haplogroup I may be mediated by downregulation of macrophage UTY and PRKY genes rather than traditional cardiovascular risk factors.
Effect estimate: 0.61- and 0.64-fold lower expression
p-value: P=0.0001 and P=0.002
OBJECTIVE: Haplogroup I of male-specific region of the human Y chromosome is associated with 50% increased risk of coronary artery disease. It is not clear to what extent conventional cardiovascular risk factors and genes of the male-specific region may explain this association. APPROACH AND RESULTS: A total of 1988 biologically unrelated men from 4 white European populations were genotyped using 11 Y chromosome single nucleotide polymorphisms and classified into 13 most common European haplogroups. Approximately 75% to 93% of the haplotypic variation of the Y chromosome in all cohorts was attributable to I, R1a, and R1b1b2 lineages. None of traditional cardiovascular risk factors, including body mass index, blood pressures, lipids, glucose, C-reactive protein, creatinine, and insulin resistance, was associated with haplogroup I of the Y chromosome in the joint inverse variance meta-analysis. Fourteen of 15 ubiquitous single-copy genes of the male-specific region were expressed in human macrophages. When compared with men with other haplogroups, carriers of haplogroup I had ≈ 0.61- and 0.64-fold lower expression of ubiquitously transcribed tetratricopeptide repeat, Y-linked gene (UTY) and protein kinase, Y-linked, pseudogene (PRKY) in macrophages (P=0.0001 and P=0.002, respectively). CONCLUSIONS: Coronary artery disease predisposing haplogroup I of the Y chromosome is associated with downregulation of UTY and PRKY genes in macrophages but not with conventional cardiovascular risk factors.
Bloomer et al. (Fri,) conducted a meta-analysis in Coronary artery disease (n=1,988). Haplogroup I of the Y chromosome vs. Other haplogroups was evaluated on Expression of UTY and PRKY genes in macrophages (0.61- and 0.64-fold lower expression, p=P=0.0001 and P=0.002). Carriers of the coronary artery disease-predisposing haplogroup I of the Y chromosome had 0.61- and 0.64-fold lower expression of UTY and PRKY genes in macrophages (P=0.0001 and P=0.002).