A. Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Medicine and Medical Specialties, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and University of Milan, Milan, Italy;
Blood. 2013 Oct 10;122(15):2555-61. doi: 10.1182/blood-2013-05-503649. Epub 2013 Aug 2.
In family studies, the risk for venous thromboembolism (VTE) in relatives with factor V Leiden (FVL) or G20210A prothrombin (PT20210A) gene polymorphisms may differ according to genotype and clinical presentation of the proband. To address this hypothesis, a retrospective cohort family study was carried out on 192 kindreds with at least one member with homozygous FVL or PT20210A, for a total of 886 relatives. The proband of the family was heterozygous in 68 and homozygous or with both polymorphisms in 124 kindreds. Twenty-three probands were asymptomatic, 11 had had arterial thrombosis, 7 obstetrical complications, and 151 venous thrombosis (122 VTE and 29 superficial vein thrombosis). The incidence of VTE (per 1000 patient-years) in relatives was higher when the proband had heterozygous rather than homozygous polymorphism (1.25 [95% confidence interval (CI), 0.73-1.91] vs 0.44 [0.19-0.78]) and when the proband had had VTE instead of other or no clinical manifestations (0.95 [0.57-1.42] vs 0.50 [0.19-0.96]). Compared with relatives belonging to kindreds with homozygous probands without VTE, the adjusted hazard ratio of VTE for relatives selected from kindreds with heterozygous probands with VTE was 4.14 (95% CI, 1.17-14.71). The genotype and clinical presentation of the proband influence the risk for VTE in relatives with FVL or PT20210A.
在家族研究中，携带因子 V 莱顿（FVL）或凝血酶原 G20210A（PT20210A）基因突变的亲属发生静脉血栓栓塞症（VTE）的风险可能因基因型和先证者的临床表现而异。为了验证这一假说，我们对 192 个至少有一个 FVL 或 PT20210A 纯合子的家系进行了回顾性队列家族研究，共涉及 886 名亲属。68 个家系的先证者为杂合子，124 个家系的先证者为纯合子或同时携带两种突变。23 名先证者无症状，11 名有动脉血栓形成，7 名有产科并发症，151 名有静脉血栓形成（122 例 VTE 和 29 例浅静脉血栓形成）。当先证者为杂合而非纯合突变时（1.25 [95%置信区间（CI），0.73-1.91] vs 0.44 [0.19-0.78]），以及当先证者发生 VTE 而非其他临床表现或无临床表现时（0.95 [0.57-1.42] vs 0.50 [0.19-0.96]），亲属发生 VTE 的发病率（每 1000 患者年的发生率）较高。与来自无 VTE 纯合先证者的家系的亲属相比，来自有 VTE 杂合先证者的家系的亲属发生 VTE 的调整后风险比为 4.14（95% CI，1.17-14.71）。先证者的基因型和临床表现影响携带 FVL 或 PT20210A 的亲属发生 VTE 的风险。
