深部静脉血栓的遗传危险因素（英文）知识介绍.pptVIP

Toshiyuki MIYATA, PhD National Cardiovascular Center Research Institute, Osaka, Japan;Advanced age is a risk for venous thromboembolism (VTE);Risk factors for venous thromboembolismN Engl J Med, 358, 1037-52, 2008;;;Protein S K196E as a Risk for VTE;;;Heterozygotes;Acquired factors influencing plasma protein S activity; PROS1 K196E mutation is a genetic risk factor for venous thromboembolism (VTE) in Japanese. A missense mutation causing Lys196 to be replaced by Glu is located within the 2nd EGF-like domain. The odds ratio of the mutant E allele for VTE was 5.58. Individuals heterozygous for the mutant E-allele had lower (mean 16%) plasma protein S activity than wildtype subjects. ;The allelic frequency of the E allele was 0.9%. We estimated a total of as many as 10,000 Japanese as homozygotes. A substantial proportion of the Japanese population carries the PROS1 E allele and is at risk of developing VTE. Therefore, individuals with the PROS1 E allele should avoid environmental risk factors known to be associated with VTE.;;Methods: We have sequenced the entire coding regions of 3 genes in all 173 DNA samples obtained from Japanese VTE patients without any consideration of their activities and antigen levels. ;Number of Mutation Carriers;PS K196E mutation as a modifier;5’UTR;Comparison of first onset age of VTE events between mutation carriers and non-carriers;Recurrent mutations found in Japanese VTE patients;;;Acknowledgements;