Advanced

Genetic and epigenetic factors are associated with expression of respiratory chain component NDUFB6 in human skeletal muscle

Ling, Charlotte LU ; Poulsen, Pernille; Simonsson, Stina; Rönn, Tina LU ; Holmkvist, Johan LU ; Almgren, Peter LU ; Hagert, Per LU ; Nilsson, Emma; Mabey, AmandaG LU and Nilsson, Peter LU , et al. (2007) In Journal of Clinical Investigation 117(11). p.3427-3435
Abstract
Insulin resistance and type 2 diabetes are associated with decreased expression of genes that regulate oxidative phosphorylation in skeletal muscle. To determine whether this defect might be inherited or acquired, we investigated the association of genetic, epigenetic, and nongenetic factors with expression of NDUFB6, a component of the respiratory chain that is decreased in muscle from diabetic patients. Expression of NDUFB6 was influenced by age, with lower gene expression in muscle of elderly subjects. Heritability of NDUFB6 expression in muscle was estimated to be approximately 60% in twins. A polymorphism in the NDUFB6 promoter region that creates a possible DNA methylation site (rs629566, A/G) was associated with a decline in muscle... (More)
Insulin resistance and type 2 diabetes are associated with decreased expression of genes that regulate oxidative phosphorylation in skeletal muscle. To determine whether this defect might be inherited or acquired, we investigated the association of genetic, epigenetic, and nongenetic factors with expression of NDUFB6, a component of the respiratory chain that is decreased in muscle from diabetic patients. Expression of NDUFB6 was influenced by age, with lower gene expression in muscle of elderly subjects. Heritability of NDUFB6 expression in muscle was estimated to be approximately 60% in twins. A polymorphism in the NDUFB6 promoter region that creates a possible DNA methylation site (rs629566, A/G) was associated with a decline in muscle NDUFB6 expression with age. Although young subjects with the rs629566 G/G genotype exhibited higher muscle NDUFB6 expression, this genotype was associated with reduced expression in elderly subjects. This was subsequently explained by the finding of increased DNA methylation in the promoter of elderly, but not young, subjects carrying the rs629566 G/G genotype. Furthermore, the degree of DNA methylation correlated negatively with muscle NDUFB6 expression, which in turn was associated with insulin sensitivity. Our results demonstrate that genetic, epigenetic, and nongenetic factors associate with NDUFB6 expression in human muscle and suggest that genetic and epigenetic factors may interact to increase age-dependent susceptibility to insulin resistance. (Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Clinical Investigation
volume
117
issue
11
pages
3427 - 3435
publisher
American Society for Clinical Investigation
external identifiers
  • PMID:17948130
  • WOS:000250676000035
  • Scopus:36049002392
ISSN
0021-9738
DOI
10.1172/JCI30938
language
English
LU publication?
yes
id
577df07c-08da-44c0-856f-a353be639822 (old id 1137902)
date added to LUP
2008-08-15 15:33:32
date last changed
2016-10-13 04:27:47
@misc{577df07c-08da-44c0-856f-a353be639822,
  abstract     = {Insulin resistance and type 2 diabetes are associated with decreased expression of genes that regulate oxidative phosphorylation in skeletal muscle. To determine whether this defect might be inherited or acquired, we investigated the association of genetic, epigenetic, and nongenetic factors with expression of NDUFB6, a component of the respiratory chain that is decreased in muscle from diabetic patients. Expression of NDUFB6 was influenced by age, with lower gene expression in muscle of elderly subjects. Heritability of NDUFB6 expression in muscle was estimated to be approximately 60% in twins. A polymorphism in the NDUFB6 promoter region that creates a possible DNA methylation site (rs629566, A/G) was associated with a decline in muscle NDUFB6 expression with age. Although young subjects with the rs629566 G/G genotype exhibited higher muscle NDUFB6 expression, this genotype was associated with reduced expression in elderly subjects. This was subsequently explained by the finding of increased DNA methylation in the promoter of elderly, but not young, subjects carrying the rs629566 G/G genotype. Furthermore, the degree of DNA methylation correlated negatively with muscle NDUFB6 expression, which in turn was associated with insulin sensitivity. Our results demonstrate that genetic, epigenetic, and nongenetic factors associate with NDUFB6 expression in human muscle and suggest that genetic and epigenetic factors may interact to increase age-dependent susceptibility to insulin resistance.},
  author       = {Ling, Charlotte and Poulsen, Pernille and Simonsson, Stina and Rönn, Tina and Holmkvist, Johan and Almgren, Peter and Hagert, Per and Nilsson, Emma and Mabey, AmandaG and Nilsson, Peter and Vaag, Allan and Groop, Leif},
  issn         = {0021-9738},
  language     = {eng},
  number       = {11},
  pages        = {3427--3435},
  publisher    = {ARRAY(0xaa401e0)},
  series       = {Journal of Clinical Investigation},
  title        = {Genetic and epigenetic factors are associated with expression of respiratory chain component NDUFB6 in human skeletal muscle},
  url          = {http://dx.doi.org/10.1172/JCI30938},
  volume       = {117},
  year         = {2007},
}