Male-specific region of the Y chromosome and cardiovascular risk: phylogenetic analysis and gene expression studies.
Arterioscler Thromb Vasc Biol
; 33(7): 1722-7, 2013 Jul.
Article
em En
| MEDLINE
| ID: mdl-23640493
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 ANDRESULTS:
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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Filogenia
/
Doenças Cardiovasculares
/
Cromossomos Humanos Y
Tipo de estudo:
Clinical_trials
/
Diagnostic_studies
/
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
/
Systematic_reviews
Limite:
Adolescent
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Adult
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Humans
/
Male
País/Região como assunto:
Europa
Idioma:
En
Revista:
Arterioscler Thromb Vasc Biol
Assunto da revista:
ANGIOLOGIA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Reino Unido