Abstract
BackgroundGenome-wide association study (GWAS) has reported that rs6903956 within the first intron of androgen-dependent tissue factor pathway inhibitor (TFPI) regulating protein (ADTRP) gene is associated with coronary artery disease (CAD) risk in the Chinese population. Although ADTRP is believed to be involved in the upregulation of TFPI, the underlying mechanism involved is largely unknown. This study investigated the association of rs6903956 with plasma Factor VII coagulant activity (FVIIc) and fibrinogen levels, which are regulated by TFPI and are independent risk predictors for CAD.MethodsWe conducted the analysis in both Chinese adult (N = 309) and neonatal cohorts (N = 447). The genotypes of the rs6903956 single nucleotide polymorphism (SNP) were determined by the polymerase chain reaction restriction fragment length polymorphism method (PCR–RFLP). FVIIc and fibrinogen level were measured from citrated plasma. The association between rs6903956 and coagulation factors was tested by linear regression with adjustment for possible confounders. Analysis was carried out in adults and neonates separately.ResultsNo significant association was observed between rs6903956 and plasma FVIIc nor fibrinogen levels with adjustment for age, gender, body mass index (BMI) and cigarette smoking in adults (P for FVIIc = 0.464; P for fibrinogen = 0.349). The SNP was also not associated with these two coagulation factors in the neonates (P for FVIIc = 0.579; P for fibrinogen = 0.359) after adjusting for gestational age, gender and birth weight.ConclusionsSNP rs6903956 on ADTRP gene was not associated with plasma FVIIc nor fibrinogen levels.
Highlights
Genome-wide association study (GWAS) has reported that rs6903956 within the first intron of androgen-dependent tissue factor pathway inhibitor (TFPI) regulating protein (ADTRP) gene is associated with coronary artery disease (CAD) risk in the Chinese population
As ADTRP has been found to upregulate TFPI, we hypothesized that it is likely to have an impact on key coagulation factors, such as Factor VII coagulant activity (FVIIc) and fibrinogen, which are known to have an association with CAD risk
Study population To determine the impact of the ADTRP genetic variant on plasma FVIIc and fibrinogen, we conducted the analysis in a group of healthy subjects who were free from CAD at the time of recruitment
Summary
Study population To determine the impact of the ADTRP genetic variant on plasma FVIIc and fibrinogen, we conducted the analysis in a group of healthy subjects who were free from CAD at the time of recruitment. A total of 1267 neonates were recruited from the three major ethnic groups in Singapore and of these, 447 of Chinese ethnicity with available FVIIc, fibrinogen and rs6903956 genotype information were included in our analysis. Statistical analysis Among all the study subjects recruited, 309 adults and 447 neonates had complete information for both genotypes and coagulation factor measurements, data from these participants were included in the analysis. FVIIc and fibrinogen levels were not normally distributed in both adults and neonates They were both Zscore transformed for subsequent analysis. All statistical analyses were carried out using STATA 12.0 (Stata Corp, College station, TX) and a 5% type I error was set to indicate statistical significance (two-tailed) in all analyses
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