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Analysis of the F2LR3 (PAR4) Single Nucleotide Polymorphism (rs773902) in an Indigenous Australian Population

The F2RL3 gene encoding protease activated receptor 4 (PAR4) contains a single nucleotide variant, rs773902, that is functional. The resulting PAR4 variants, Thr120, and Ala120, are known to differently affect platelet reactivity to thrombin. Significant population differences in the frequency of th...

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Autores principales: Ningtyas, Dian, Thomson, Russell J., Tarlac, Volga, Nagaraj, Shivashankar H., Hoy, Wendy, Mathews, John D., Foote, Simon J., Gardiner, Elizabeth E., Hamilton, Justin R., McMorran, Brendan J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7204273/
https://www.ncbi.nlm.nih.gov/pubmed/32425989
http://dx.doi.org/10.3389/fgene.2020.00432
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author Ningtyas, Dian
Thomson, Russell J.
Tarlac, Volga
Nagaraj, Shivashankar H.
Hoy, Wendy
Mathews, John D.
Foote, Simon J.
Gardiner, Elizabeth E.
Hamilton, Justin R.
McMorran, Brendan J.
author_facet Ningtyas, Dian
Thomson, Russell J.
Tarlac, Volga
Nagaraj, Shivashankar H.
Hoy, Wendy
Mathews, John D.
Foote, Simon J.
Gardiner, Elizabeth E.
Hamilton, Justin R.
McMorran, Brendan J.
author_sort Ningtyas, Dian
collection PubMed
description The F2RL3 gene encoding protease activated receptor 4 (PAR4) contains a single nucleotide variant, rs773902, that is functional. The resulting PAR4 variants, Thr120, and Ala120, are known to differently affect platelet reactivity to thrombin. Significant population differences in the frequency of the allele indicate it may be an important determinant in the ethnic differences that exist in thrombosis and hemostasis, and for patient outcomes to PAR antagonist anti-platelet therapies. Here we determined the frequency of rs773902 in an Indigenous Australian group comprising 467 individuals from the Tiwi Islands. These people experience high rates of renal disease that may be related to platelet and PAR4 function and are potential recipients of PAR-antagonist treatments. The rs773902 minor allele frequency (Thr120) in the Tiwi Islanders was 0.32, which is similar to European and Asian groups and substantially lower than Melanesians and some African groups. Logistic regression and allele distortion testing revealed no significant associations between the variant and several markers of renal function, as well as blood glucose and blood pressure. These findings suggest that rs773902 is not an important determinant for renal disease in this Indigenous Australian group. However, the relationships between rs773902 genotype and platelet and drug responsiveness in the Tiwi, and the allele frequency in other Indigenous Australian groups should be evaluated.
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spelling pubmed-72042732020-05-18 Analysis of the F2LR3 (PAR4) Single Nucleotide Polymorphism (rs773902) in an Indigenous Australian Population Ningtyas, Dian Thomson, Russell J. Tarlac, Volga Nagaraj, Shivashankar H. Hoy, Wendy Mathews, John D. Foote, Simon J. Gardiner, Elizabeth E. Hamilton, Justin R. McMorran, Brendan J. Front Genet Genetics The F2RL3 gene encoding protease activated receptor 4 (PAR4) contains a single nucleotide variant, rs773902, that is functional. The resulting PAR4 variants, Thr120, and Ala120, are known to differently affect platelet reactivity to thrombin. Significant population differences in the frequency of the allele indicate it may be an important determinant in the ethnic differences that exist in thrombosis and hemostasis, and for patient outcomes to PAR antagonist anti-platelet therapies. Here we determined the frequency of rs773902 in an Indigenous Australian group comprising 467 individuals from the Tiwi Islands. These people experience high rates of renal disease that may be related to platelet and PAR4 function and are potential recipients of PAR-antagonist treatments. The rs773902 minor allele frequency (Thr120) in the Tiwi Islanders was 0.32, which is similar to European and Asian groups and substantially lower than Melanesians and some African groups. Logistic regression and allele distortion testing revealed no significant associations between the variant and several markers of renal function, as well as blood glucose and blood pressure. These findings suggest that rs773902 is not an important determinant for renal disease in this Indigenous Australian group. However, the relationships between rs773902 genotype and platelet and drug responsiveness in the Tiwi, and the allele frequency in other Indigenous Australian groups should be evaluated. Frontiers Media S.A. 2020-04-30 /pmc/articles/PMC7204273/ /pubmed/32425989 http://dx.doi.org/10.3389/fgene.2020.00432 Text en Copyright © 2020 Ningtyas, Thomson, Tarlac, Nagaraj, Hoy, Mathews, Foote, Gardiner, Hamilton and McMorran. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Ningtyas, Dian
Thomson, Russell J.
Tarlac, Volga
Nagaraj, Shivashankar H.
Hoy, Wendy
Mathews, John D.
Foote, Simon J.
Gardiner, Elizabeth E.
Hamilton, Justin R.
McMorran, Brendan J.
Analysis of the F2LR3 (PAR4) Single Nucleotide Polymorphism (rs773902) in an Indigenous Australian Population
title Analysis of the F2LR3 (PAR4) Single Nucleotide Polymorphism (rs773902) in an Indigenous Australian Population
title_full Analysis of the F2LR3 (PAR4) Single Nucleotide Polymorphism (rs773902) in an Indigenous Australian Population
title_fullStr Analysis of the F2LR3 (PAR4) Single Nucleotide Polymorphism (rs773902) in an Indigenous Australian Population
title_full_unstemmed Analysis of the F2LR3 (PAR4) Single Nucleotide Polymorphism (rs773902) in an Indigenous Australian Population
title_short Analysis of the F2LR3 (PAR4) Single Nucleotide Polymorphism (rs773902) in an Indigenous Australian Population
title_sort analysis of the f2lr3 (par4) single nucleotide polymorphism (rs773902) in an indigenous australian population
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7204273/
https://www.ncbi.nlm.nih.gov/pubmed/32425989
http://dx.doi.org/10.3389/fgene.2020.00432
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