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Genetic Variants Associated With Glycine Metabolism and Their Role in Insulin Sensitivity and Type 2 Diabetes

Xie, Weijia; Wood, Andrew R.; Lyssenko, Valeriya LU ; Weedon, Michael N.; Knowles, Joshua W.; Alkayyali, Sami LU ; Assimes, Themistocles L.; Quertermous, Thomas; Abbasi, Fahim and Paananen, Jussi, et al. (2013) In Diabetes 62(6). p.2141-2150
Abstract
Circulating metabolites associated with insulin sensitivity may represent useful biomarkers, but their causal role in insulin sensitivity and diabetes is less certain. We previously identified novel metabolites correlated with insulin sensitivity measured by the hyperinsulinemic-euglycemic clamp. The top-ranking metabolites were in the glutathione and glycine biosynthesis pathways. We aimed to identify common genetic variants associated with metabolites in these pathways and test their role in insulin sensitivity and type 2 diabetes. With 1,004 nondiabetic individuals from the RISC study, we performed a genome-wide association study (GWAS) of 14 insulin sensitivity-related metabolites and one metabolite ratio. We replicated our results in... (More)
Circulating metabolites associated with insulin sensitivity may represent useful biomarkers, but their causal role in insulin sensitivity and diabetes is less certain. We previously identified novel metabolites correlated with insulin sensitivity measured by the hyperinsulinemic-euglycemic clamp. The top-ranking metabolites were in the glutathione and glycine biosynthesis pathways. We aimed to identify common genetic variants associated with metabolites in these pathways and test their role in insulin sensitivity and type 2 diabetes. With 1,004 nondiabetic individuals from the RISC study, we performed a genome-wide association study (GWAS) of 14 insulin sensitivity-related metabolites and one metabolite ratio. We replicated our results in the Botnia study (n = 342). We assessed the association of these variants with diabetes-related traits in GWAS meta-analyses (GENESIS [including RISC, EUGENE2, and Stanford], MAGIC, and DIAGRAM). We identified four associations with three metabolites-glycine (rs715 at CPS1), serine (rs478093 at PHGDH), and betaine (rs499368 at SLC6A12; rs17823642 at BHMT)-and one association signal with glycine-to-serine ratio (rs1107366 at ALDH1L1). There was no robust evidence for association between these variants and insulin resistance or diabetes. Genetic variants associated with genes in the glycine biosynthesis pathways do not provide consistent evidence for a role of glycine in diabetes-related traits. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes
volume
62
issue
6
pages
2141 - 2150
publisher
American Diabetes Association Inc.
external identifiers
  • wos:000319845000047
  • scopus:84878256943
ISSN
1939-327X
DOI
10.2337/db12-0876
language
English
LU publication?
yes
id
81102c4a-d2e7-47bb-af95-6ffb1b76e6d2 (old id 3927077)
date added to LUP
2013-08-01 07:35:11
date last changed
2018-12-16 04:10:54
@article{81102c4a-d2e7-47bb-af95-6ffb1b76e6d2,
  abstract     = {Circulating metabolites associated with insulin sensitivity may represent useful biomarkers, but their causal role in insulin sensitivity and diabetes is less certain. We previously identified novel metabolites correlated with insulin sensitivity measured by the hyperinsulinemic-euglycemic clamp. The top-ranking metabolites were in the glutathione and glycine biosynthesis pathways. We aimed to identify common genetic variants associated with metabolites in these pathways and test their role in insulin sensitivity and type 2 diabetes. With 1,004 nondiabetic individuals from the RISC study, we performed a genome-wide association study (GWAS) of 14 insulin sensitivity-related metabolites and one metabolite ratio. We replicated our results in the Botnia study (n = 342). We assessed the association of these variants with diabetes-related traits in GWAS meta-analyses (GENESIS [including RISC, EUGENE2, and Stanford], MAGIC, and DIAGRAM). We identified four associations with three metabolites-glycine (rs715 at CPS1), serine (rs478093 at PHGDH), and betaine (rs499368 at SLC6A12; rs17823642 at BHMT)-and one association signal with glycine-to-serine ratio (rs1107366 at ALDH1L1). There was no robust evidence for association between these variants and insulin resistance or diabetes. Genetic variants associated with genes in the glycine biosynthesis pathways do not provide consistent evidence for a role of glycine in diabetes-related traits.},
  author       = {Xie, Weijia and Wood, Andrew R. and Lyssenko, Valeriya and Weedon, Michael N. and Knowles, Joshua W. and Alkayyali, Sami and Assimes, Themistocles L. and Quertermous, Thomas and Abbasi, Fahim and Paananen, Jussi and Haering, Hans and Hansen, Torben and Pedersen, Oluf and Smith, Ulf and Laakso, Markku and Dekker, Jacqueline M. and Nolan, John J. and Groop, Leif and Ferrannini, Ele and Adam, Klaus-Peter and Gall, Walter E. and Frayling, Timothy M. and Walker, Mark},
  issn         = {1939-327X},
  language     = {eng},
  number       = {6},
  pages        = {2141--2150},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  title        = {Genetic Variants Associated With Glycine Metabolism and Their Role in Insulin Sensitivity and Type 2 Diabetes},
  url          = {http://dx.doi.org/10.2337/db12-0876},
  volume       = {62},
  year         = {2013},
}