The Level Of Coagulation Factor â…« In Chinese Healthy Population And Its Genetics

BackgroundIt has been reported that the average activity of coagulation factor XII depends on the ethnicity of the population under study but little information is available on Chinese. We here provide an analysis of the range of activities and antigenic levels of factor XII in healthy Han Chinese and correlate the measurements with polymorphisms and mutations in the corresponding gene.MethodsFor our study, we recruited healthy Han Chinese individuals,16 years old or older, from among people visiting Peking Union Medical College Hospital for routine check-ups over a period of four months. All eligible subjects agreed to participate in the study and gave written informed consent. Subjects with abnormal renal or liver function or positive lupus anticoagulant, individuals receiving anticoagulant therapy or hormone therapy, as well as pregnant women were excluded. The study was approved by the Ethics Committee of Peking Union Medical College Hospital and University, Beijing, China. Plasma samples were obtained from 549 healthy Chinese adults (264 men,285 women; age 16-79 years) undergoing routine check-ups. The samples were subjected to an activated partial thromboplastin time-based factor XII activity assay as well as an enzyme-linked immunosorbent assay. Partial gene sequence analyses were performed in subjects with low factor XII activity and in normal controls.ResultsNinety-five percent of the subjects had factor XII activities between 47% and 160.25%, with no evidence for an influence of sex or age. Among 15 subjects with activity levels <47%, we found one novel nonsense and two missense mutations that may lead to dysfunctional proteins. No mutations were found in a selection of subjects with activities above 47%. Interestingly, however, the particular sequence at a known C/T polymorphism at position 46 just upstream of the translational start codon was correlated with factor XII activity. Subjects homozygous for the T allele, which has an allelic frequency of 0.69, showed significantly lower factor XII activities compared to subjects homozygous for the C allele or those heterozygous for C/T.ConclusionsThe survey determined the normal range of factor XII activities in healthy Chinese and identified mutations as well as a biased representation of a polymorphic nucleotide in subjects with abnormally low activities. The results provide an essential basis for the diagnosis of Fâ…« deficiencies in Chinese.