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Arterioscler Thromb Vasc Biol. 2013 Jul;33(7):1722-7. doi: 10.1161/ATVBAHA.113.301608. Epub 2013 May 2.

Male-specific region of the Y chromosome and cardiovascular risk: phylogenetic analysis and gene expression studies.

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  • 1Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom.

Abstract

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.

KEYWORDS:

DNA; association; cardiovascular risk; gene; genetics; mRNA

PMID:
23640493
[PubMed - indexed for MEDLINE]
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