Touzé Emmanuel, Rothwell Peter M
Stroke Prevention Research Unit, University Department of Clinical Neurology, Radcliffe Infirmary, Oxford OX2 6HE, UK.
Lancet Neurol. 2007 Feb;6(2):125-33. doi: 10.1016/S1474-4422(06)70683-4.
Ischaemic stroke is partly heritable. However, although the genetic and non-genetic factors responsible could be sex-specific, interactions between the sex of the parent affected and the sex of the proband or affected siblings are unknown. We sought to assess the relation between the sex and phenotype of affected probands and the sex of affected first-degree relatives.
We determined the prevalence of history of stroke in the mother, father, and other first-degree relatives in female and male probands with ischaemic stroke or transient ischaemic attack in the population-based Oxford Vascular Study (OXVASC). We validated our findings using unpublished individual patient data from two independent Oxford studies.
In OXVASC, detailed family history was available in 806 (93%) probands. Female probands were more likely than males to have at least one affected first-degree relative (146/423 vs 104/383; OR 1.4, 95% CI 1.1-2.0, p=0.02) due entirely to an excess of affected female relatives in female probands (female relative vs male relative OR=1.7, 1.3-2.4, p=0.0004; female only vs male only OR=2.1, 1.4-3.1, p=0.0001). Maternal stroke was more common than paternal stroke in female probands (OR=1.8, 1.2-2.7, p=0.001) but not in males (OR=1.1, 0.7-1.7, p=0.38), and female probands were more likely than males to have an affected sister (OR=3.1, 1.5-6.7, p=0.004) but not an affected brother (OR=1.1, 0.6-2.1, p=0.80). Ages at first stroke were also correlated within families among affected females (r=0.36, p=0.004) but not among affected males, such that the excess of affected female relatives of female probands was greatest when the difference in age at first stroke was less than 5 years (OR=3.7, 1.6-8.6, p=0.0007) and fell as the age difference increased (p for trend=0.004). These findings were independent of traditional risk factors and stroke subtype. Data from the other Oxford studies confirmed the excess maternal history of stroke in female probands (OR=2.3, 1.5-3.8, p<0.00001) and the lack in males (OR=1.0, 0.7-1.4, p=0.58).
Heritability of ischaemic stroke is greater in women than in men, with an excess of affected mothers and affected sisters in female probands independent of traditional vascular risk factors, which could be explained by sex-specific genetic, epigenetic, or non-genetic mechanisms.
缺血性中风具有部分遗传性。然而，尽管相关的遗传和非遗传因素可能存在性别差异，但受影响父母的性别与先证者或受影响兄弟姐妹的性别之间的相互作用尚不清楚。我们试图评估受影响先证者的性别和表型与受影响一级亲属的性别之间的关系。
在基于人群的牛津血管研究（OXVASC）中，我们确定了患有缺血性中风或短暂性脑缺血发作的女性和男性先证者的母亲、父亲及其他一级亲属的中风病史患病率。我们使用来自两项独立牛津研究的未发表的个体患者数据对我们的发现进行了验证。
在OXVASC中，806名（93%）先证者有详细的家族史。女性先证者比男性先证者更有可能至少有一名受影响的一级亲属（146/423对104/383；比值比1.4，95%置信区间1.1 - 2.0，p = 0.02），这完全是由于女性先证者中受影响的女性亲属过多（女性亲属与男性亲属相比，比值比 = 1.7，1.3 - 2.4，p = 0.0004；仅女性受影响与仅男性受影响相比，比值比 = 2.1，1.4 - 3.1，p = 0.0001）。在女性先证者中，母亲中风比父亲中风更常见（比值比 = 1.8，1.2 - 2.7，p = 0.001），而在男性先证者中并非如此（比值比 = 1.1，0.7 - 1.7，p = 0.38），并且女性先证者比男性先证者更有可能有受影响的姐妹（比值比 = 3.1，1.5 - 6.7，p = 0.004），但不太可能有受影响的兄弟（比值比 = 1.1，0.6 - 2.1，p = 0.80）。首次中风的年龄在受影响的女性家庭成员之间也具有相关性（r = 0.36，p = 0.
