title: R147W mutation of PROC gene is common in venous thrombotic patients in Taiwanese Chinese.
abstract: We analyzed the genetic defects of 21 unrelated patients with venous thrombosis in whom hereditary protein C deficiency was diagnosed. Eleven mutations were detected in 18 families, while no mutation was detectable in the other three families. Among these mutations, a common genetic mutation of protein C (PROC) gene recurred in 43% (nine propositi from these 21 families). This C6152T mutation at exon 7 resulted in a missense mutation, Arg147Trp (R147W). Each propositus or family carrier had another specific polymorphism T66C at exon 2, which did not change the proline at position (-21). The haplotype analysis strongly suggested a founder effect. The first thrombotic attack was significantly younger in patients with multiple genetic defects or combined with other risk factors than those without precipitating factors. We further studied the prevalence rate of R147W mutations in normal populations through PCR amplification and dot hybridization. Three different cohorts got similar results. The prevalence rate of R147W in health controls is 0.85% [95% confidence interval (CI) 0.35-1.35]. Analysis of plasma protein C levels of all patients or carriers suggested that R147W was a type II deficiency. The odds ratio of thrombosis of R147W is 5.1 (95% CI 1.7-14.8). Taken together, R147W mutation is a significant thrombotic risk factor and is the most common defect of PROC gene in Taiwanese patients with protein C deficiency. This finding is important for screening thrombophilic families in Chinese populations.
authors.affiliation: Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan. woei@ha.mc.ntu.edu.tw
authors.forename: Woei
authors.initials: W
authors.lastname: Tsay
authors.forename: Ming-Ching
authors.initials: MC
authors.lastname: Shen
mesh_terms: D000293:Adolescent; D000328:Adult; D006801:Humans; D008875:Middle Aged; D020125:Mutation, Missense; D015995:Prevalence; D011401:Promoter Regions, Genetic / Q000235:genetics; D011486:Protein C / Q000235:genetics*; D020151:Protein C Deficiency / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D013624:Taiwan / Q000453:epidemiology; D020246:Venous Thrombosis / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*
chemical_list: D011486:Protein C