title: Male-specific risk of first and recurrent venous thrombosis: a phylogenetic analysis of the Y chromosome.
abstract: Essentials Men have an unexplained higher risk of a first and recurrent venous thrombosis (VT) than women. We studied the role of the major European Y chromosome haplogroups in first and recurrent VT. In contrast to a study on coronary artery disease, haplogroup I was not linked to VT risk. Haplogroup E-carriers may have an increased risk of recurrent VT, but a larger study is needed.
  
  
  
  Background The risk of venous thrombosis (VT) recurrence is higher in men than in women. When reproductive risk factors are excluded, this sex difference is also apparent for a first VT. The current explanations for this difference are insufficient. Objectives To study the association between chromosome Y haplogroups and the risks of a first and recurrent VT. Methods Y chromosomes of 3742 men (1729 patients; 2013 controls) from the MEGA case-control study were tracked into haplogroups according to the phylogenetic tree. We calculated the risk of a first VT by comparing the major haplogroups with the most frequent haplogroup. For recurrence risk, 1645 patients were followed for a mean of 5 years, during which 350 developed a recurrence (21%; MEGA follow-up study). We calculated recurrence rates for the major haplogroups, and compared groups by calculating hazard ratios. Results We observed 13 haplogroups, of which R1b was the most frequent (59%). The major haplogroups were not associated with a first VT, with odds ratios ranging from 1.01 to 1.15. Haplogroup E carriers had the highest recurrence rate (53.5 per 1000 person-years, 95% confidence interval [CI] 33.3-86.1), whereas haplogroup R1a carriers had the lowest recurrence rate (24.3 per 1000 person-years, 95% CI 12.6-46.6). As compared with haplogroup R1b carriers, both haplogroups were not significantly associated with recurrence risk. Conclusions In contrast to a study on coronary artery disease, our results do not show a clear predisposing effect of Y haplogroups on first and recurrent VT risk in men. It is therefore unlikely that Y variation can explain the sex difference in VT risk.
authors: Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
authors: H G
authors: HG
authors: de Haan
authors: Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
authors: A
authors: A
authors: van Hylckama Vlieg
authors: Forensic Laboratory for DNA Research, Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors: K J
authors: KJ
authors: van der Gaag
authors: Forensic Laboratory for DNA Research, Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors: P
authors: P
authors: de Knijff
authors: Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands. f.r.rosendaal@lumc.nl.|Einthoven Laboratory of Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands. f.r.rosendaal@lumc.nl.|Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands. f.r.rosendaal@lumc.nl.
authors: F R
authors: FR
authors: Rosendaal
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002874:Chromosome Mapping; D041322:Chromosomes, Human, Y / Q000235:genetics*; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D014644:Genetic Variation; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D016017:Odds Ratio; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011655:Pulmonary Embolism / Q000097:blood / Q000235:genetics; D012008:Recurrence; D012307:Risk Factors; D012737:Sex Factors; D020246:Venous Thrombosis / Q000097:blood*; D044465:White People / Q000235:genetics
keywords: Y chromosome; genetic variation; recurrence; risk factors; venous thrombosis