Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Forensic Laboratory for DNA Research, Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
J Thromb Haemost. 2016 Oct;14(10):1971-1977. doi: 10.1111/jth.13437. Epub 2016 Oct 12.
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.
研究 Y 染色体单倍群与首发和复发性静脉血栓栓塞症（VT）风险的关系。
根据系统进化树，对来自 MEGA 病例对照研究的 3742 名男性（1729 名患者；2013 名对照）的 Y 染色体进行单倍群追踪。我们通过比较主要单倍群与最常见单倍群，计算首发 VT 的风险。对于复发风险，对 1645 名患者进行了平均 5 年的随访，其中 350 名患者复发（MEGA 随访研究）。我们计算了主要单倍群的复发率，并通过计算风险比来比较各组。
共观察到 13 种单倍群，其中 R1b 最为常见（59%）。主要单倍群与首发 VT 无关，比值比范围为 1.01-1.15。E 单倍群携带者的复发率最高（53.5/1000 人年，95%置信区间 [CI] 33.3-86.1），而 R1a 单倍群携带者的复发率最低（24.3/1000 人年，95% CI 12.6-46.6）。与 R1b 单倍群携带者相比，两种单倍群与复发风险均无显著相关性。
与一项关于冠心病的研究相反，我们的研究结果并未显示 Y 染色体单倍群对男性首发和复发性 VT 风险有明显的易感性。因此，Y 变异不太可能解释 VT 风险的性别差异。
