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A possible role for miRNA silencing in disease phenotype variation in Swedish transthyretin V30M carriers

BACKGROUND: Familial amyloidosis with polyneuropathy (FAP) is an autosomal dominant disease caused by transthyretin (TTR) mutations, of which V30M (TTR c.148G > A, p.Val50Met, "Val30Met") is the most common. Swedish V30M carriers display later age at onset and lower penetrance compared...

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Autores principales: Olsson, Malin, Norgren, Nina, Obayashi, Konen, Plante-Bordeneuve, Violaine, Suhr, Ole B, Cederquist, Kristina, Jonasson, Jenni
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2945965/
https://www.ncbi.nlm.nih.gov/pubmed/20840742
http://dx.doi.org/10.1186/1471-2350-11-130
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author Olsson, Malin
Norgren, Nina
Obayashi, Konen
Plante-Bordeneuve, Violaine
Suhr, Ole B
Cederquist, Kristina
Jonasson, Jenni
author_facet Olsson, Malin
Norgren, Nina
Obayashi, Konen
Plante-Bordeneuve, Violaine
Suhr, Ole B
Cederquist, Kristina
Jonasson, Jenni
author_sort Olsson, Malin
collection PubMed
description BACKGROUND: Familial amyloidosis with polyneuropathy (FAP) is an autosomal dominant disease caused by transthyretin (TTR) mutations, of which V30M (TTR c.148G > A, p.Val50Met, "Val30Met") is the most common. Swedish V30M carriers display later age at onset and lower penetrance compared to other populations. METHODS: In the study, 130 Swedish V30M carriers (32 early, 30 late onset and 68 asymptomatic carriers) and 50 controls, 23 French symptomatic V30M carriers and 29 controls and 18 Japanese symptomatic V30M carriers and 29 controls were included. We aimed to identify additional genetic factors in the TTR gene and its surrounding region that could have an impact on phenotype. RESULTS: We identified three SNPs (rs71383038, rs3794885 and rs62093482) with a significant difference in allele frequency between Swedish V30M carriers and controls. The two Swedish V30M homozygous patients present in the study also displayed homozygosity for the CA10 (rs71383038), A (rs3794885) and T (rs62093482) alleles in these SNPs. Hence, these alleles are present on the Swedish V30M haplotype. Of these, rs62093482 is located in the 3'UTR of TTR gene and thus more interesting since SNPs in the 3'UTR can affect gene expression levels by modifying microRNA (miRNA) targeting activity. miRNA target predictions revealed four potential miRNAs with predicted targets unique for the polymorphic allele. CONCLUSIONS: Our results are the first to show the presence of a 3'UTR polymorphism on the V30M haplotype in Swedish carriers, which can serve as a miRNA binding site potentially leading to down-regulated expression from the mutated TTR allele. This finding may be related to the low penetrance and high age at onset of the disease observed in the Swedish patient population.
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spelling pubmed-29459652010-09-28 A possible role for miRNA silencing in disease phenotype variation in Swedish transthyretin V30M carriers Olsson, Malin Norgren, Nina Obayashi, Konen Plante-Bordeneuve, Violaine Suhr, Ole B Cederquist, Kristina Jonasson, Jenni BMC Med Genet Research Article BACKGROUND: Familial amyloidosis with polyneuropathy (FAP) is an autosomal dominant disease caused by transthyretin (TTR) mutations, of which V30M (TTR c.148G > A, p.Val50Met, "Val30Met") is the most common. Swedish V30M carriers display later age at onset and lower penetrance compared to other populations. METHODS: In the study, 130 Swedish V30M carriers (32 early, 30 late onset and 68 asymptomatic carriers) and 50 controls, 23 French symptomatic V30M carriers and 29 controls and 18 Japanese symptomatic V30M carriers and 29 controls were included. We aimed to identify additional genetic factors in the TTR gene and its surrounding region that could have an impact on phenotype. RESULTS: We identified three SNPs (rs71383038, rs3794885 and rs62093482) with a significant difference in allele frequency between Swedish V30M carriers and controls. The two Swedish V30M homozygous patients present in the study also displayed homozygosity for the CA10 (rs71383038), A (rs3794885) and T (rs62093482) alleles in these SNPs. Hence, these alleles are present on the Swedish V30M haplotype. Of these, rs62093482 is located in the 3'UTR of TTR gene and thus more interesting since SNPs in the 3'UTR can affect gene expression levels by modifying microRNA (miRNA) targeting activity. miRNA target predictions revealed four potential miRNAs with predicted targets unique for the polymorphic allele. CONCLUSIONS: Our results are the first to show the presence of a 3'UTR polymorphism on the V30M haplotype in Swedish carriers, which can serve as a miRNA binding site potentially leading to down-regulated expression from the mutated TTR allele. This finding may be related to the low penetrance and high age at onset of the disease observed in the Swedish patient population. BioMed Central 2010-09-14 /pmc/articles/PMC2945965/ /pubmed/20840742 http://dx.doi.org/10.1186/1471-2350-11-130 Text en Copyright ©2010 Olsson et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Olsson, Malin
Norgren, Nina
Obayashi, Konen
Plante-Bordeneuve, Violaine
Suhr, Ole B
Cederquist, Kristina
Jonasson, Jenni
A possible role for miRNA silencing in disease phenotype variation in Swedish transthyretin V30M carriers
title A possible role for miRNA silencing in disease phenotype variation in Swedish transthyretin V30M carriers
title_full A possible role for miRNA silencing in disease phenotype variation in Swedish transthyretin V30M carriers
title_fullStr A possible role for miRNA silencing in disease phenotype variation in Swedish transthyretin V30M carriers
title_full_unstemmed A possible role for miRNA silencing in disease phenotype variation in Swedish transthyretin V30M carriers
title_short A possible role for miRNA silencing in disease phenotype variation in Swedish transthyretin V30M carriers
title_sort possible role for mirna silencing in disease phenotype variation in swedish transthyretin v30m carriers
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2945965/
https://www.ncbi.nlm.nih.gov/pubmed/20840742
http://dx.doi.org/10.1186/1471-2350-11-130
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