Possible race and gender divergence in association of genetic variations with plasma von Willebrand factor: a study of ARIC and 1000 genome cohorts.
The synthesis, secretion and clearance of von Willebrand factor (VWF) are regulated by genetic variations in coding and promoter regions of the VWF gene. We have previously identified 19 single nucleotide polymorphisms (SNPs), primarily in introns that are associated with VWF antigen levels in subjects of European descent. In this study, we conducted race by gender analyses to compare the association of VWF SNPs with VWF antigen among 10,434 healthy Americans of European (EA) or African (AA) descent from the Atherosclerosis Risk in Communities (ARIC) study. Among 75 SNPs analyzed, 13 and 10 SNPs were associated with VWF antigen levels in EA male and EA female subjects, respectively. However, only one SNP (RS1063857) was significantly associated with VWF antigen in AA females and none was in AA males. Haplotype analysis of the ARIC samples and studying racial diversities in the VWF gene from the 1000 genomes database suggest a greater degree of variations in the VWF gene in AA subjects as compared to EA subjects. Together, these data suggest potential race and gender divergence in regulating VWF expression by genetic variations.
State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, CAMS & PUMC, Beijing, China.
Zhou
Z
Zhou
Human Genome Sequencing Center, Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, Texas, United States of America ; Institute of Neurology, Tianjin Medical University General Hospital, Tianjin, China.
Fuli
F
Yu
Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina, United States of America.
Ashley
A
Buchanan
State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, CAMS & PUMC, Beijing, China.
Yuanyuan
Y
Fu
Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, Texas, United States of America.
Marco
M
Campos
National Health Research Institutes, Taipei, Taiwan.
Kenneth K
KK
Wu
Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina, United States of America.
Lloyd E
LE
Chambless
Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States of America.
Aaron R
AR
Folsom
Human Genetic Center, University of Texas School of Public Health, Houston, Texas, United States of America.
Eric
E
Boerwinkle
Puget Sound Blood Research Institute, Puget Sound Blood Center, Seattle, Washington, United States of America ; Division of Hematology, Department of Medicine, University of Washington School of Medicine, Seattle, Washington, United States of America.
Jing-fei
JF
Dong
D050197:Atherosclerosis / Q000235:genetics*; D044383:Black People / Q000235:genetics*; D015331:Cohort Studies; D003710:Demography; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D014644:Genetic Variation; D015894:Genome, Human / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012727:Sex Characteristics; D044465:White People / Q000235:genetics*; D014841:von Willebrand Factor / Q000235:genetics*
D014841:von Willebrand Factor