Zivelin Ariella, Mor-Cohen Ronit, Kovalsky Victoria, Kornbrot Nurit, Conard Jacqueline, Peyvandi Flora, Kyrle Paul A, Bertina Rogier, Peyvandi Ferial, Emmerich Joseph, Seligsohn Uri
The Amalia Biron Research Institute of Thrombosis and Hemostasis, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel.
Blood. 2006 Jun 15;107(12):4666-8. doi: 10.1182/blood-2005-12-5158. Epub 2006 Feb 21.
Prothrombin 20210G>A and factor V Leiden are common prothrombotic mutations in whites for which founder effects have been established. In this study, we analyzed the frequencies of 5 single nucleotide polymorphisms (SNPs) and 9 microsatellites flanking the prothrombin gene (F2) in 88 homozygotes for 20210A and 66 homozygotes for 20210G. For estimating the age of the prothrombin 20210G>A mutation, we used the DMLE+2.0 program, which analyzed linkage disequilibria between the mutation and the multiple markers that had been assessed. This analysis yielded an age estimate of 23,720 years (95% credible set, 19,080-31,340 years). A similar analysis by the DMLE+2.0 program was performed on 5 SNPs from previously studied homozygotes for factor V Leiden and controls that yielded an age estimate of 21,340 years (95% credible set, 16,880-29,480 years). The occurrence of the 2 mutations in whites toward the end of the last glaciation and their presently wide distribution in whites suggest selective evolutionary advantages for which some evidence was reported (diminished blood loss) or is controversial (protection against infections).
凝血酶原20210G>A和因子V莱顿突变是白人中常见的促血栓形成突变，其奠基者效应已得到证实。在本研究中，我们分析了88例20210A纯合子和66例20210G纯合子中凝血酶原基因（F2）侧翼的5个单核苷酸多态性（SNP）和9个微卫星的频率。为了估计凝血酶原20210G>A突变的发生时间，我们使用了DMLE+2.0程序，该程序分析了该突变与已评估的多个标记之间的连锁不平衡。该分析得出的年龄估计为23720年（95%可信区间，19080 - 31340年）。对先前研究的因子V莱顿纯合子和对照的5个SNP进行了DMLE+2.0程序的类似分析，得出的年龄估计为21340年（95%可信区间，16880 - 29480年）。这两种突变在白人中于末次冰期结束时出现，且目前在白人中广泛分布，这表明存在选择性进化优势，对此有一些证据报道（失血减少），或存在争议（预防感染）。
