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Association between genetic variants in the Coenzyme Q(10 )metabolism and Coenzyme Q(10 )status in humans

BACKGROUND: Coenzyme Q(10 )(CoQ(10)) is essential for mitochondrial energy production and serves as an antioxidants in extra mitochondrial membranes. The genetics of primary CoQ(10 )deficiency has been described in several studies, whereas the influence of common genetic variants on CoQ(10 )status i...

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Autores principales: Fischer, Alexandra, Schmelzer, Constance, Rimbach, Gerald, Niklowitz, Petra, Menke, Thomas, Döring, Frank
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3160390/
https://www.ncbi.nlm.nih.gov/pubmed/21774831
http://dx.doi.org/10.1186/1756-0500-4-245
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author Fischer, Alexandra
Schmelzer, Constance
Rimbach, Gerald
Niklowitz, Petra
Menke, Thomas
Döring, Frank
author_facet Fischer, Alexandra
Schmelzer, Constance
Rimbach, Gerald
Niklowitz, Petra
Menke, Thomas
Döring, Frank
author_sort Fischer, Alexandra
collection PubMed
description BACKGROUND: Coenzyme Q(10 )(CoQ(10)) is essential for mitochondrial energy production and serves as an antioxidants in extra mitochondrial membranes. The genetics of primary CoQ(10 )deficiency has been described in several studies, whereas the influence of common genetic variants on CoQ(10 )status is largely unknown. Here we tested for non-synonymous single-nucleotidepolymorphisms (SNP) in genes involved in the biosynthesis (CoQ3(G272S ), CoQ6(M406V), CoQ7(M103T)), reduction (NQO1(P187S), NQO2(L47F)) and metabolism (apoE3/4) of CoQ(10 )and their association with CoQ(10 )status. For this purpose, CoQ(10 )serum levels of 54 healthy male volunteers were determined before (T(0)) and after a 14 days supplementation (T(14)) with 150 mg/d of the reduced form of CoQ(10). FINDINGS: At T(0), the CoQ(10 )level of heterozygous NQO1(P187S )carriers were significantly lower than homozygous S/S carriers (0.93 ± 0.25 μM versus 1.34 ± 0.42 μM, p = 0.044). For this polymorphism a structure homology-based method (PolyPhen) revealed a possibly damaging effect on NQO1 protein activity. Furthermore, CoQ(10 )plasma levels were significantly increased in apoE4/E4 genotype after supplementation in comparison to apoE2/E3 genotype (5.93 ± 0.151 μM versus 4.38 ± 0.792 μM, p = 0.034). Likewise heterozygous CoQ3(G272S )carriers had higher CoQ(10 )plasma levels at T(14 )compared to G/G carriers but this difference did not reach significance (5.30 ± 0.96 μM versus 4.42 ± 1.67 μM, p = 0.082). CONCLUSIONS: In conclusion, our pilot study provides evidence that NQO1(P187S )and apoE polymorphisms influence CoQ(10 )status in humans.
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spelling pubmed-31603902011-08-24 Association between genetic variants in the Coenzyme Q(10 )metabolism and Coenzyme Q(10 )status in humans Fischer, Alexandra Schmelzer, Constance Rimbach, Gerald Niklowitz, Petra Menke, Thomas Döring, Frank BMC Res Notes Short Report BACKGROUND: Coenzyme Q(10 )(CoQ(10)) is essential for mitochondrial energy production and serves as an antioxidants in extra mitochondrial membranes. The genetics of primary CoQ(10 )deficiency has been described in several studies, whereas the influence of common genetic variants on CoQ(10 )status is largely unknown. Here we tested for non-synonymous single-nucleotidepolymorphisms (SNP) in genes involved in the biosynthesis (CoQ3(G272S ), CoQ6(M406V), CoQ7(M103T)), reduction (NQO1(P187S), NQO2(L47F)) and metabolism (apoE3/4) of CoQ(10 )and their association with CoQ(10 )status. For this purpose, CoQ(10 )serum levels of 54 healthy male volunteers were determined before (T(0)) and after a 14 days supplementation (T(14)) with 150 mg/d of the reduced form of CoQ(10). FINDINGS: At T(0), the CoQ(10 )level of heterozygous NQO1(P187S )carriers were significantly lower than homozygous S/S carriers (0.93 ± 0.25 μM versus 1.34 ± 0.42 μM, p = 0.044). For this polymorphism a structure homology-based method (PolyPhen) revealed a possibly damaging effect on NQO1 protein activity. Furthermore, CoQ(10 )plasma levels were significantly increased in apoE4/E4 genotype after supplementation in comparison to apoE2/E3 genotype (5.93 ± 0.151 μM versus 4.38 ± 0.792 μM, p = 0.034). Likewise heterozygous CoQ3(G272S )carriers had higher CoQ(10 )plasma levels at T(14 )compared to G/G carriers but this difference did not reach significance (5.30 ± 0.96 μM versus 4.42 ± 1.67 μM, p = 0.082). CONCLUSIONS: In conclusion, our pilot study provides evidence that NQO1(P187S )and apoE polymorphisms influence CoQ(10 )status in humans. BioMed Central 2011-07-21 /pmc/articles/PMC3160390/ /pubmed/21774831 http://dx.doi.org/10.1186/1756-0500-4-245 Text en Copyright ©2011 Döring 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 Short Report
Fischer, Alexandra
Schmelzer, Constance
Rimbach, Gerald
Niklowitz, Petra
Menke, Thomas
Döring, Frank
Association between genetic variants in the Coenzyme Q(10 )metabolism and Coenzyme Q(10 )status in humans
title Association between genetic variants in the Coenzyme Q(10 )metabolism and Coenzyme Q(10 )status in humans
title_full Association between genetic variants in the Coenzyme Q(10 )metabolism and Coenzyme Q(10 )status in humans
title_fullStr Association between genetic variants in the Coenzyme Q(10 )metabolism and Coenzyme Q(10 )status in humans
title_full_unstemmed Association between genetic variants in the Coenzyme Q(10 )metabolism and Coenzyme Q(10 )status in humans
title_short Association between genetic variants in the Coenzyme Q(10 )metabolism and Coenzyme Q(10 )status in humans
title_sort association between genetic variants in the coenzyme q(10 )metabolism and coenzyme q(10 )status in humans
topic Short Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3160390/
https://www.ncbi.nlm.nih.gov/pubmed/21774831
http://dx.doi.org/10.1186/1756-0500-4-245
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