Prothrombin 20210G>A is an ancestral prothrombotic mutation that occurred in whites approximately 24 000 years ago

• Published in: Blood Vol. 107; no. 12; pp. 4666 - 4668
• Main Authors: Zivelin, Ariella, Mor-Cohen, Ronit, Kovalsky, Victoria, Kornbrot, Nurit, Conard, Jacqueline, Peyvandi, Flora, Kyrle, Paul A., Bertina, Rogier, Peyvandi, Ferial, Emmerich, Joseph, Seligsohn, Uri
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.06.2006; The Americain Society of Hematology
• Subjects: Biological and medical sciences; DNA Mutational Analysis; European Continental Ancestry Group; Evolution, Molecular; Factor V - genetics; Female; Founder Effect; Hematologic and hematopoietic diseases; Homozygote; Humans; Linkage Disequilibrium; Male; Medical sciences; Platelet diseases and coagulopathies; Point Mutation; Prothrombin - genetics; Software; Vascular disease; Human; Age estimation; Factor V Leiden; Prothrombin; Cardiovascular disease; Mutation; Thrombosis
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2005-12-5158

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).