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KIF6 Trp719Arg Genetic Variant Increases Risk for Thoracic Aortic Dissection

Background: KIF6 (kinesin family member 6), a protein coded by the KIF6 gene, serves an important intracellular function to transport organelles along microtubules. In a pilot study, we found that a common KIF6 Trp719Arg variant increased the propensity of thoracic aortic aneurysms (TAA) to suffer d...

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Autores principales: Velasco, Juan J., Li, Yupeng, Ziganshin, Bulat A., Zafar, Mohammad A., Rizzo, John A., Ma, Deqiong, Zang, Hui, Kalyanasundaram, Asanish, Elefteriades, John A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9956195/
https://www.ncbi.nlm.nih.gov/pubmed/36833179
http://dx.doi.org/10.3390/genes14020252
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author Velasco, Juan J.
Li, Yupeng
Ziganshin, Bulat A.
Zafar, Mohammad A.
Rizzo, John A.
Ma, Deqiong
Zang, Hui
Kalyanasundaram, Asanish
Elefteriades, John A.
author_facet Velasco, Juan J.
Li, Yupeng
Ziganshin, Bulat A.
Zafar, Mohammad A.
Rizzo, John A.
Ma, Deqiong
Zang, Hui
Kalyanasundaram, Asanish
Elefteriades, John A.
author_sort Velasco, Juan J.
collection PubMed
description Background: KIF6 (kinesin family member 6), a protein coded by the KIF6 gene, serves an important intracellular function to transport organelles along microtubules. In a pilot study, we found that a common KIF6 Trp719Arg variant increased the propensity of thoracic aortic aneurysms (TAA) to suffer dissection (AD). The present study aims for a definite investigation of the predictive ability of KIF6 719Arg vis à vis AD. Confirmatory findings would enhance natural history prediction in TAA. Methods: 1108 subjects (899 aneurysm and 209 dissection patients) had KIF6 719Arg variant status determined. Results: The 719Arg variant in the KIF6 gene correlated strongly with occurrence of AD. Specifically, KIF6 719Arg positivity (homozygous or heterozygous) was substantially more common in dissectors (69.8%) than non-dissectors (58.5%) (p = 0.003). Odds ratios (OR) for suffering aortic dissection ranged from 1.77 to 1.94 for Arg carriers in various dissection categories. These high OR associations were noted for both ascending and descending aneurysms and for homozygous and heterozygous Arg variant patients. The rate of aortic dissection over time was significantly higher for carriers of the Arg allele (p = 0.004). Additionally, Arg allele carriers were more likely to reach the combined endpoint of dissection or death (p = 0.03). Conclusions: We demonstrate the marked adverse impact of the 719Arg variant of the KIF6 gene on the likelihood that a TAA patient will suffer aortic dissection. Clinical assessment of the variant status of this molecularly important gene may provide a valuable “non-size” criterion to enhance surgical decision making above and beyond the currently used metric of aortic size (diameter).
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spelling pubmed-99561952023-02-25 KIF6 Trp719Arg Genetic Variant Increases Risk for Thoracic Aortic Dissection Velasco, Juan J. Li, Yupeng Ziganshin, Bulat A. Zafar, Mohammad A. Rizzo, John A. Ma, Deqiong Zang, Hui Kalyanasundaram, Asanish Elefteriades, John A. Genes (Basel) Article Background: KIF6 (kinesin family member 6), a protein coded by the KIF6 gene, serves an important intracellular function to transport organelles along microtubules. In a pilot study, we found that a common KIF6 Trp719Arg variant increased the propensity of thoracic aortic aneurysms (TAA) to suffer dissection (AD). The present study aims for a definite investigation of the predictive ability of KIF6 719Arg vis à vis AD. Confirmatory findings would enhance natural history prediction in TAA. Methods: 1108 subjects (899 aneurysm and 209 dissection patients) had KIF6 719Arg variant status determined. Results: The 719Arg variant in the KIF6 gene correlated strongly with occurrence of AD. Specifically, KIF6 719Arg positivity (homozygous or heterozygous) was substantially more common in dissectors (69.8%) than non-dissectors (58.5%) (p = 0.003). Odds ratios (OR) for suffering aortic dissection ranged from 1.77 to 1.94 for Arg carriers in various dissection categories. These high OR associations were noted for both ascending and descending aneurysms and for homozygous and heterozygous Arg variant patients. The rate of aortic dissection over time was significantly higher for carriers of the Arg allele (p = 0.004). Additionally, Arg allele carriers were more likely to reach the combined endpoint of dissection or death (p = 0.03). Conclusions: We demonstrate the marked adverse impact of the 719Arg variant of the KIF6 gene on the likelihood that a TAA patient will suffer aortic dissection. Clinical assessment of the variant status of this molecularly important gene may provide a valuable “non-size” criterion to enhance surgical decision making above and beyond the currently used metric of aortic size (diameter). MDPI 2023-01-18 /pmc/articles/PMC9956195/ /pubmed/36833179 http://dx.doi.org/10.3390/genes14020252 Text en © 2023 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
Velasco, Juan J.
Li, Yupeng
Ziganshin, Bulat A.
Zafar, Mohammad A.
Rizzo, John A.
Ma, Deqiong
Zang, Hui
Kalyanasundaram, Asanish
Elefteriades, John A.
KIF6 Trp719Arg Genetic Variant Increases Risk for Thoracic Aortic Dissection
title KIF6 Trp719Arg Genetic Variant Increases Risk for Thoracic Aortic Dissection
title_full KIF6 Trp719Arg Genetic Variant Increases Risk for Thoracic Aortic Dissection
title_fullStr KIF6 Trp719Arg Genetic Variant Increases Risk for Thoracic Aortic Dissection
title_full_unstemmed KIF6 Trp719Arg Genetic Variant Increases Risk for Thoracic Aortic Dissection
title_short KIF6 Trp719Arg Genetic Variant Increases Risk for Thoracic Aortic Dissection
title_sort kif6 trp719arg genetic variant increases risk for thoracic aortic dissection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9956195/
https://www.ncbi.nlm.nih.gov/pubmed/36833179
http://dx.doi.org/10.3390/genes14020252
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