| Summary: | (1) Background: The purpose of this study was to evaluate the effect of gene polymorphisms on prothrombin time (PT) and activated partial thromboplastin time (APTT) in a healthy Chinese population. (2) Methods: A total of 403 healthy volunteers from a series of novel oral anticoagulants (NOACs) bioequivalence trials in China were included. Coagulation tests for PT and APTT were performed in the central lab at Peking University First Hospital. Whole-exome sequencing (WES) and genome-wide association analysis were performed. (3) Results: In the correlation analysis of PT, 105 SNPs from 84 genes reached the genome-wide significance threshold (<i>p</i> < 1 × 10<sup>−5</sup>). Zinc Finger Protein 594 (<i>ZNF594</i>) rs184838268 (<i>p</i> = 4.50 × 10<sup>−19</sup>) was most significantly related to PT, and Actinin Alpha 1 (<i>ACTN1</i>) was found to interact most with other candidate genes. Significant associations with previously reported candidate genes Aurora Kinase B (<i>AURKB</i>), Complement C5(<i>C5</i>), Clock Circadian Regulator (<i>CLOCK</i>), and Histone Deacetylase 9(<i>HDAC9</i>) were detected in our dataset (<i>p</i> < 1 × 10<sup>−5</sup>). PiggyBac Transposable Element Derived 2(<i>PGBD2</i>) rs75935520 (<i>p</i> = 4.49 × 10<sup>−6</sup>), Bromodomain Adjacent To Zinc Finger Domain 2A(<i>BAZ2A</i>) rs199970765 (<i>p</i> = 5.69 × 10<sup>−6</sup>) and Protogenin (<i>PRTG</i>) rs80064850 (<i>p</i> = 8.69 × 10<sup>−6</sup>) were significantly correlated with APTT (<i>p</i> < 1 × 10<sup>−5</sup>). The heritability values of PT and APTT were 0.83 and 0.64, respectively; (4) Conclusion: The PT and APTT of healthy populations are affected by genetic polymorphisms. <i>ZNF594</i> and <i>ACTN1</i> variants could be novel genetic markers of PT, while <i>PRTG</i> polymorphisms might be associated with APTT levels. The findings could be attributed to ethnic differences, and need further investigation.
|
|---|