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Increased Risk of Multiple Outpatient Surgeries in African-American Carriers of Transthyretin Val122Ile Mutation Is Modulated by Non-Coding Variants
Background: African-Americans (AAs) have a 3.5% carrier prevalence of Transthyretin (TTR) Val122Ile mutation (rs76992529), which is the genetic cause of a hereditary form of amyloidosis. Methods: We investigated the medical history of Val122Ile carriers and assessed the role of a non-coding variatio...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406512/ https://www.ncbi.nlm.nih.gov/pubmed/30813263 http://dx.doi.org/10.3390/jcm8020269 |
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author | Polimanti, Renato Nuñez, Yaira Z. Gelernter, Joel |
author_facet | Polimanti, Renato Nuñez, Yaira Z. Gelernter, Joel |
author_sort | Polimanti, Renato |
collection | PubMed |
description | Background: African-Americans (AAs) have a 3.5% carrier prevalence of Transthyretin (TTR) Val122Ile mutation (rs76992529), which is the genetic cause of a hereditary form of amyloidosis. Methods: We investigated the medical history of Val122Ile carriers and assessed the role of a non-coding variation in 4361 unrelated AAs. Results: We observed that the Ile122 allele was associated with a 6.8-fold increase in the odds of having 10 or more outpatient surgeries (p = 7.81 × 10(−5)). Stratifying the analysis by sex, the Ile122 allele was associated with a 15.2-fold increase in the odds of having 10 or more outpatient surgeries in men (p = 6.49 × 10(−7)). A similar sex difference was observed with respect to the association of Val122Ile with musculoskeletal and connective-tissue disorders in an independent cohort of British subjects (n = 361,194, p = 2.47 × 10(−13); n(male) = 167,020, p(male) = 4.02 × 10(−24)). In Val122Ile African-American carriers, we observed that haplotypes in the upstream region regulating TTR hepatic expression are associated with having 10 or more outpatient surgeries (p = 2.56 × 10(−9)). Conclusions: TTR Val122Ile showed a large effect with respect to an extreme phenotype identified in medical history that may be related to osteoarthritis, an early sign of the disease. Additionally, the non-coding variation appears to accelerate the negative consequences associated with Val122Ile mutation via TTR expression regulation. |
format | Online Article Text |
id | pubmed-6406512 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-64065122019-03-22 Increased Risk of Multiple Outpatient Surgeries in African-American Carriers of Transthyretin Val122Ile Mutation Is Modulated by Non-Coding Variants Polimanti, Renato Nuñez, Yaira Z. Gelernter, Joel J Clin Med Article Background: African-Americans (AAs) have a 3.5% carrier prevalence of Transthyretin (TTR) Val122Ile mutation (rs76992529), which is the genetic cause of a hereditary form of amyloidosis. Methods: We investigated the medical history of Val122Ile carriers and assessed the role of a non-coding variation in 4361 unrelated AAs. Results: We observed that the Ile122 allele was associated with a 6.8-fold increase in the odds of having 10 or more outpatient surgeries (p = 7.81 × 10(−5)). Stratifying the analysis by sex, the Ile122 allele was associated with a 15.2-fold increase in the odds of having 10 or more outpatient surgeries in men (p = 6.49 × 10(−7)). A similar sex difference was observed with respect to the association of Val122Ile with musculoskeletal and connective-tissue disorders in an independent cohort of British subjects (n = 361,194, p = 2.47 × 10(−13); n(male) = 167,020, p(male) = 4.02 × 10(−24)). In Val122Ile African-American carriers, we observed that haplotypes in the upstream region regulating TTR hepatic expression are associated with having 10 or more outpatient surgeries (p = 2.56 × 10(−9)). Conclusions: TTR Val122Ile showed a large effect with respect to an extreme phenotype identified in medical history that may be related to osteoarthritis, an early sign of the disease. Additionally, the non-coding variation appears to accelerate the negative consequences associated with Val122Ile mutation via TTR expression regulation. MDPI 2019-02-22 /pmc/articles/PMC6406512/ /pubmed/30813263 http://dx.doi.org/10.3390/jcm8020269 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Polimanti, Renato Nuñez, Yaira Z. Gelernter, Joel Increased Risk of Multiple Outpatient Surgeries in African-American Carriers of Transthyretin Val122Ile Mutation Is Modulated by Non-Coding Variants |
title | Increased Risk of Multiple Outpatient Surgeries in African-American Carriers of Transthyretin Val122Ile Mutation Is Modulated by Non-Coding Variants |
title_full | Increased Risk of Multiple Outpatient Surgeries in African-American Carriers of Transthyretin Val122Ile Mutation Is Modulated by Non-Coding Variants |
title_fullStr | Increased Risk of Multiple Outpatient Surgeries in African-American Carriers of Transthyretin Val122Ile Mutation Is Modulated by Non-Coding Variants |
title_full_unstemmed | Increased Risk of Multiple Outpatient Surgeries in African-American Carriers of Transthyretin Val122Ile Mutation Is Modulated by Non-Coding Variants |
title_short | Increased Risk of Multiple Outpatient Surgeries in African-American Carriers of Transthyretin Val122Ile Mutation Is Modulated by Non-Coding Variants |
title_sort | increased risk of multiple outpatient surgeries in african-american carriers of transthyretin val122ile mutation is modulated by non-coding variants |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406512/ https://www.ncbi.nlm.nih.gov/pubmed/30813263 http://dx.doi.org/10.3390/jcm8020269 |
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