A genetic association study of activated partial thromboplastin time in European Americans and African Americans: the ARIC Study

Abstract

Reduced activated partial thromboplastin time (aPTT) is a risk marker for incident and recurrent venous thromboembolism (VTE). Genetic factors influencing aPTT are not well understood, especially in populations of non-European ancestry. The present study aimed to identify aPTT-related gene variants in both European Americans (EAs) and African Americans (AAs). We conducted a genetic association study for aPTT in 9719 EAs and 2799 AAs from the Atherosclerosis Risk in Communities (ARIC) study. Using the Candidate Gene Association Resource (CARe) consortium candidate gene array, the analyses were based on ∼50 000 SNPs in ∼2000 candidate genes. In EAs, the analyses identified a new independent association for aPTT in F5 (rs2239852, P-value = 1.9 × 10(-8)), which clusters with a coding variant rs6030 (P-value = 7.8 × 10(-7)). The remaining significant signals were located on F5, HRG, KNG1, F11, F12 and ABO and have been previously reported in EA populations. In AAs, significant signals were identified in KNG1, HRG, F12, ABO and VWF, with the leading variants in KNG1, HRG and F12 being the same as in the EAs; the significant variant in VWF (rs2229446, P-value = 1.2 × 10(-6)) was specific to the AA sample (minor allele frequency = 19% in AAs and 0.2% in EAs) and has not been previously reported. This is the first study to report aPTT-related genetic variants in AAs. Our findings in AAs demonstrate transferability of previously reported associations with KNG1, HRG and F12 in EAs. We also identified new associations at F5 in EAs and VWF in AAs that have not been previously reported for aPTT.

Gestational diabetes mellitus is associated with antenatal hypercoagulability and secondary hyperfibrinolysis: a case control study of Chinese women

“…The maternity center is located in a small city in China that has relatively few population migrations, and most of the participants in this study were local residents. As previously reported [34] , the influence of ethnicity on coagulation might exist that could be excluded in our study.…”

“…The shortening of APTT in type 2 diabetic patients has been described as indicating a high risk of a hypercoagulable state [31] . It has also been shown that the increase in fibrinogen and the reduction in fibrinolytic activity in GDM are more similar to the changes present in type 2 than in type 1 diabetic patients [32] , and it is thought that a shorter APTT is a marker of venous thromboembolism risk [33,34] .…”

Molecular basis of coronary artery dilation and aneurysms in patients with Kawasaki disease based on differential protein expression

“…However, some studies have indicated that they may interact with each other in the coagulation pathway. KNG1 and HRG have similar structures and are adjacent to each other on chromosome 3, which suggests that these proteins may exhibit similar functions ( 24 , 25 ). HRG deficiency is associated with enhanced blood coagulation, which indicates that decreased KNG1 is a potential cofactor to enhance coagulation ( 26 ).…”

Gestational diabetes mellitus is associated with antenatal hypercoagulability and secondary hyperfibrinolysis: a case control study of Chinese women

“…The shortening of APTT in type 2 diabetic patients has been described as indicating a high risk of a hypercoagulable state [29] . It has also been shown that the increase in fibrinogen and the reduction in fibrinolytic activity in GDM are more similar to the changes present in type 2 than in type 1 diabetic patients [30] , and it is thought that a shorter APTT is a marker of venous thromboembolism risk [31,32] .…”

“…The maternity center is located in a small city in China that has relatively small population mobility, and most of the participants in the study were local residents. These characteristics of the study participants exclude the influence of ethnicity on coagulation that has been previously reported [32] . In addition, we used different methods to assess CFA at the same time point and the results were consistent.…”