title: Male-specific region of the Y chromosome and cardiovascular risk: phylogenetic analysis and gene expression studies.
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.
  
  
  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.
authors: Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom.
authors: Lisa D S
authors: LD
authors: Bloomer
authors: Christopher P
authors: CP
authors: Nelson
authors: James
authors: J
authors: Eales
authors: Matthew
authors: M
authors: Denniff
authors: Paraskevi
authors: P
authors: Christofidou
authors: Radoslaw
authors: R
authors: Debiec
authors: Jasbir
authors: J
authors: Moore
authors: Ewa
authors: E
authors: Zukowska-Szczechowska
authors: Alison H
authors: AH
authors: Goodall
authors: John
authors: J
authors: Thompson
authors: Nilesh J
authors: NJ
authors: Samani
authors: Fadi J
authors: FJ
authors: Charchar
authors: Maciej
authors: M
authors: Tomaszewski
mesh_terms: D000293:Adolescent; D000328:Adult; D062186:Arterial Pressure / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D041322:Chromosomes, Human, Y; D005060:Europe; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D016014:Linear Models; D008264:Macrophages / Q000378:metabolism; D008297:Male; D015778:Minor Histocompatibility Antigens; D009687:Nuclear Proteins / Q000235:genetics; D016017:Odds Ratio; D010641:Phenotype; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011544:Pseudogenes; D018570:Risk Assessment; D012307:Risk Factors; D012737:Sex Factors; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D015415:Biomarkers; D015778:Minor Histocompatibility Antigens; D009687:Nuclear Proteins; C484453:UTY protein, human; C109449:PRKY protein, human; D017346:Protein Serine-Threonine Kinases
keywords: DNA; association; cardiovascular risk; gene; genetics; mRNA