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Genetic Polymorphisms Associated with Prothrombin Time and Activated Partial Thromboplastin Time in Chinese Healthy Population
(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) bioe...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9602091/ https://www.ncbi.nlm.nih.gov/pubmed/36292752 http://dx.doi.org/10.3390/genes13101867 |
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author | Zhang, Fan Mu, Guangyan Liu, Zhiyan Xie, Qiufen Zhang, Hanxu Zhou, Shuang Wang, Zhe Hu, Kun Wang, Zining Zhao, Xia Cui, Yimin Xiang, Qian |
author_facet | Zhang, Fan Mu, Guangyan Liu, Zhiyan Xie, Qiufen Zhang, Hanxu Zhou, Shuang Wang, Zhe Hu, Kun Wang, Zining Zhao, Xia Cui, Yimin Xiang, Qian |
author_sort | Zhang, Fan |
collection | PubMed |
description | (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 (p < 1 × 10(−5)). Zinc Finger Protein 594 (ZNF594) rs184838268 (p = 4.50 × 10(−19)) was most significantly related to PT, and Actinin Alpha 1 (ACTN1) was found to interact most with other candidate genes. Significant associations with previously reported candidate genes Aurora Kinase B (AURKB), Complement C5(C5), Clock Circadian Regulator (CLOCK), and Histone Deacetylase 9(HDAC9) were detected in our dataset (p < 1 × 10(−5)). PiggyBac Transposable Element Derived 2(PGBD2) rs75935520 (p = 4.49 × 10(−6)), Bromodomain Adjacent To Zinc Finger Domain 2A(BAZ2A) rs199970765 (p = 5.69 × 10(−6)) and Protogenin (PRTG) rs80064850 (p = 8.69 × 10(−6)) were significantly correlated with APTT (p < 1 × 10(−5)). 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. ZNF594 and ACTN1 variants could be novel genetic markers of PT, while PRTG polymorphisms might be associated with APTT levels. The findings could be attributed to ethnic differences, and need further investigation. |
format | Online Article Text |
id | pubmed-9602091 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96020912022-10-27 Genetic Polymorphisms Associated with Prothrombin Time and Activated Partial Thromboplastin Time in Chinese Healthy Population Zhang, Fan Mu, Guangyan Liu, Zhiyan Xie, Qiufen Zhang, Hanxu Zhou, Shuang Wang, Zhe Hu, Kun Wang, Zining Zhao, Xia Cui, Yimin Xiang, Qian Genes (Basel) Article (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 (p < 1 × 10(−5)). Zinc Finger Protein 594 (ZNF594) rs184838268 (p = 4.50 × 10(−19)) was most significantly related to PT, and Actinin Alpha 1 (ACTN1) was found to interact most with other candidate genes. Significant associations with previously reported candidate genes Aurora Kinase B (AURKB), Complement C5(C5), Clock Circadian Regulator (CLOCK), and Histone Deacetylase 9(HDAC9) were detected in our dataset (p < 1 × 10(−5)). PiggyBac Transposable Element Derived 2(PGBD2) rs75935520 (p = 4.49 × 10(−6)), Bromodomain Adjacent To Zinc Finger Domain 2A(BAZ2A) rs199970765 (p = 5.69 × 10(−6)) and Protogenin (PRTG) rs80064850 (p = 8.69 × 10(−6)) were significantly correlated with APTT (p < 1 × 10(−5)). 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. ZNF594 and ACTN1 variants could be novel genetic markers of PT, while PRTG polymorphisms might be associated with APTT levels. The findings could be attributed to ethnic differences, and need further investigation. MDPI 2022-10-15 /pmc/articles/PMC9602091/ /pubmed/36292752 http://dx.doi.org/10.3390/genes13101867 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Zhang, Fan Mu, Guangyan Liu, Zhiyan Xie, Qiufen Zhang, Hanxu Zhou, Shuang Wang, Zhe Hu, Kun Wang, Zining Zhao, Xia Cui, Yimin Xiang, Qian Genetic Polymorphisms Associated with Prothrombin Time and Activated Partial Thromboplastin Time in Chinese Healthy Population |
title | Genetic Polymorphisms Associated with Prothrombin Time and Activated Partial Thromboplastin Time in Chinese Healthy Population |
title_full | Genetic Polymorphisms Associated with Prothrombin Time and Activated Partial Thromboplastin Time in Chinese Healthy Population |
title_fullStr | Genetic Polymorphisms Associated with Prothrombin Time and Activated Partial Thromboplastin Time in Chinese Healthy Population |
title_full_unstemmed | Genetic Polymorphisms Associated with Prothrombin Time and Activated Partial Thromboplastin Time in Chinese Healthy Population |
title_short | Genetic Polymorphisms Associated with Prothrombin Time and Activated Partial Thromboplastin Time in Chinese Healthy Population |
title_sort | genetic polymorphisms associated with prothrombin time and activated partial thromboplastin time in chinese healthy population |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9602091/ https://www.ncbi.nlm.nih.gov/pubmed/36292752 http://dx.doi.org/10.3390/genes13101867 |
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