PMID- 22095239
OWN - NLM
STAT- MEDLINE
DCOM- 20120619
LR  - 20211021
IS  - 1432-0428 (Electronic)
IS  - 0012-186X (Linking)
VI  - 55
IP  - 2
DP  - 2012 Feb
TI  - Common variation in oxidative phosphorylation genes is not a major cause of 
      insulin resistance or type 2 diabetes.
PG  - 340-8
LID - 10.1007/s00125-011-2377-0 [doi]
AB  - AIMS/HYPOTHESIS: There is substantial evidence that mitochondrial dysfunction is 
      linked to insulin resistance and is present in several tissues relevant to the 
      pathogenesis of type 2 diabetes. Here, we examined whether common variation in 
      genes involved in oxidative phosphorylation (OxPhos) contributes to type 2 
      diabetes susceptibility or influences diabetes-related metabolic traits. METHODS: 
      OxPhos gene variants (n = 10) that had been nominally associated (p < 0.01) with 
      type 2 diabetes in a recent genome-wide meta-analysis (n = 10,108) were selected 
      for follow-up in 3,599 type 2 diabetic and 4,956 glucose-tolerant Danish 
      individuals. A meta-analysis of these variants was performed in 11,729 type 2 
      diabetic patients and 43,943 non-diabetic individuals. The impact on OGTT-derived 
      metabolic traits was evaluated in 5,869 treatment-naive individuals from the 
      Danish Inter99 study. RESULTS: The minor alleles of COX10 rs9915302 (p = 0.02) 
      and COX5B rs1466100 (p = 0.005) showed nominal association with type 2 diabetes 
      in our Danish cohort. However, in the meta-analysis, none of the investigated 
      variants showed a robust association with type 2 diabetes after correction for 
      multiple testing. Among the alleles potentially associated with type 2 diabetes, 
      none negatively influenced surrogate markers of insulin sensitivity in 
      non-diabetic participants, while the minor alleles of UQCRC1 rs2228561 and COX10 
      rs10521253 showed a weak (p < 0.01 to p < 0.05) negative influence on indices of 
      glucose-stimulated insulin secretion. CONCLUSIONS/INTERPRETATION: We cannot rule 
      out the possibility that common variants in or near OxPhos genes may influence 
      beta cell function in non-diabetic individuals. However, our quantitative trait 
      studies and a sufficiently large meta-analysis indicate that common variation in 
      proximity to the examined OxPhos genes is not a major cause of insulin resistance 
      or type 2 diabetes.
FAU - Snogdal, L S
AU  - Snogdal LS
AD  - Diabetes Research Centre, Department of Endocrinology, Odense University 
      Hospital, Klovervaenget 6, 4th Floor, 5000 Odense, Denmark.
FAU - Wod, M
AU  - Wod M
FAU - Grarup, N
AU  - Grarup N
FAU - Vestmar, M
AU  - Vestmar M
FAU - Sparso, T
AU  - Sparso T
FAU - Jorgensen, T
AU  - Jorgensen T
FAU - Lauritzen, T
AU  - Lauritzen T
FAU - Beck-Nielsen, H
AU  - Beck-Nielsen H
FAU - Henriksen, J E
AU  - Henriksen JE
FAU - Pedersen, O
AU  - Pedersen O
FAU - Hansen, T
AU  - Hansen T
FAU - Hojlund, K
AU  - Hojlund K
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
DEP - 20111118
PL  - Germany
TA  - Diabetologia
JT  - Diabetologia
JID - 0006777
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
RN  - IY9XDZ35W2 (Glucose)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Alleles
MH  - Case-Control Studies
MH  - Denmark
MH  - Diabetes Mellitus, Type 2/*blood/genetics/*metabolism
MH  - Electron Transport Complex IV/*genetics
MH  - *Genetic Variation
MH  - Glucose/metabolism
MH  - Humans
MH  - *Insulin Resistance
MH  - Mitochondria/metabolism
MH  - Models, Biological
MH  - Models, Genetic
MH  - Oxidative Phosphorylation
MH  - Oxygen/*chemistry
MH  - Phosphorylation
MH  - *Polymorphism, Single Nucleotide
MH  - Quantitative Trait Loci
EDAT- 2011/11/19 06:00
MHDA- 2012/06/20 06:00
CRDT- 2011/11/19 06:00
PHST- 2011/09/09 00:00 [received]
PHST- 2011/10/25 00:00 [accepted]
PHST- 2011/11/19 06:00 [entrez]
PHST- 2011/11/19 06:00 [pubmed]
PHST- 2012/06/20 06:00 [medline]
AID - 10.1007/s00125-011-2377-0 [doi]
PST - ppublish
SO  - Diabetologia. 2012 Feb;55(2):340-8. doi: 10.1007/s00125-011-2377-0. Epub 2011 Nov 
      18.