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Two common genetic variants near nuclear encoded OXPHOS genes are associated with insulin secretion in vivo.

Olsson, Anders H LU ; Rönn, Tina LU ; Ladenvall, Claes LU ; Parikh, Hemang; Isomaa, Bo; Groop, Leif LU and Ling, Charlotte LU (2011) In European Journal of Endocrinology 164(5). p.765-771
Abstract
Context Mitochondrial ATP production is important in the regulation of glucose-stimulated insulin secretion. Genetic factors may modulate the capacity of the β-cells to secrete insulin and thereby contribute to the risk of type 2 diabetes. OBJECTIVE: The aim of this study was to identify genetic loci in or adjacent to nuclear encoded genes of the oxidative phosphorylation (OXPHOS) pathway that are associated with insulin secretion in vivo. DESIGN AND METHODS: To find polymorphisms associated with glucose-stimulated insulin secretion, data from a genome-wide association study (GWAS) of 1467 non-diabetic individuals, the Diabetes Genetic Initiative (DGI), was examined. 413 single nucleotide polymorphisms (SNPs) with a minor allele frequency... (More)
Context Mitochondrial ATP production is important in the regulation of glucose-stimulated insulin secretion. Genetic factors may modulate the capacity of the β-cells to secrete insulin and thereby contribute to the risk of type 2 diabetes. OBJECTIVE: The aim of this study was to identify genetic loci in or adjacent to nuclear encoded genes of the oxidative phosphorylation (OXPHOS) pathway that are associated with insulin secretion in vivo. DESIGN AND METHODS: To find polymorphisms associated with glucose-stimulated insulin secretion, data from a genome-wide association study (GWAS) of 1467 non-diabetic individuals, the Diabetes Genetic Initiative (DGI), was examined. 413 single nucleotide polymorphisms (SNPs) with a minor allele frequency (MAF) ≥0.05 located in or adjacent to 76 OXPHOS genes were included in the DGI GWAS. A more extensive population based study of 4323 non-diabetics, the PPP-Botnia, was used as a replication cohort. Insulinogenic index during an oral glucose tolerance test (OGTT) was used as a surrogate marker of glucose-stimulated insulin secretion. Multivariate linear regression analyses were used to test genotype-phenotype associations. RESULTS: Two common variants were indentified in the DGI, where the major C-allele of rs606164, adjacent to NDUFC2 (NADH dehyrogenase (ubiqinone) 1 subunit C2), and the minor G-allele of rs1323070, adjacent to COX7A2 (cythochrome c oxidase subunit VIIa polypeptide 2), showed nominal associations with decreased glucose-stimulated insulin secretion (p=0.0009 respective p=0.003). These associations were replicated in PPP-Botnia (p=0.002 and p=0.05). CONCLUSION: Our study shows that genetic variation near genes involved in oxidative phosphorylation may influence glucose-stimulated insulin secretion in vivo. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
European Journal of Endocrinology
volume
164
issue
5
pages
765 - 771
publisher
Society of the European Journal of Endocrinology
external identifiers
  • wos:000289846200014
  • pmid:21325017
  • scopus:79955540995
ISSN
1479-683X
DOI
10.1530/EJE-10-0995
language
English
LU publication?
yes
id
7e964bf0-f452-47a5-adab-778152ba01b9 (old id 1831761)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21325017?dopt=Abstract
date added to LUP
2011-03-01 15:44:58
date last changed
2017-08-06 03:24:42
@article{7e964bf0-f452-47a5-adab-778152ba01b9,
  abstract     = {Context Mitochondrial ATP production is important in the regulation of glucose-stimulated insulin secretion. Genetic factors may modulate the capacity of the β-cells to secrete insulin and thereby contribute to the risk of type 2 diabetes. OBJECTIVE: The aim of this study was to identify genetic loci in or adjacent to nuclear encoded genes of the oxidative phosphorylation (OXPHOS) pathway that are associated with insulin secretion in vivo. DESIGN AND METHODS: To find polymorphisms associated with glucose-stimulated insulin secretion, data from a genome-wide association study (GWAS) of 1467 non-diabetic individuals, the Diabetes Genetic Initiative (DGI), was examined. 413 single nucleotide polymorphisms (SNPs) with a minor allele frequency (MAF) ≥0.05 located in or adjacent to 76 OXPHOS genes were included in the DGI GWAS. A more extensive population based study of 4323 non-diabetics, the PPP-Botnia, was used as a replication cohort. Insulinogenic index during an oral glucose tolerance test (OGTT) was used as a surrogate marker of glucose-stimulated insulin secretion. Multivariate linear regression analyses were used to test genotype-phenotype associations. RESULTS: Two common variants were indentified in the DGI, where the major C-allele of rs606164, adjacent to NDUFC2 (NADH dehyrogenase (ubiqinone) 1 subunit C2), and the minor G-allele of rs1323070, adjacent to COX7A2 (cythochrome c oxidase subunit VIIa polypeptide 2), showed nominal associations with decreased glucose-stimulated insulin secretion (p=0.0009 respective p=0.003). These associations were replicated in PPP-Botnia (p=0.002 and p=0.05). CONCLUSION: Our study shows that genetic variation near genes involved in oxidative phosphorylation may influence glucose-stimulated insulin secretion in vivo.},
  author       = {Olsson, Anders H and Rönn, Tina and Ladenvall, Claes and Parikh, Hemang and Isomaa, Bo and Groop, Leif and Ling, Charlotte},
  issn         = {1479-683X},
  language     = {eng},
  number       = {5},
  pages        = {765--771},
  publisher    = {Society of the European Journal of Endocrinology},
  series       = {European Journal of Endocrinology},
  title        = {Two common genetic variants near nuclear encoded OXPHOS genes are associated with insulin secretion in vivo.},
  url          = {http://dx.doi.org/10.1530/EJE-10-0995},
  volume       = {164},
  year         = {2011},
}