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Xie, W.* ; Wood, A.R.* ; Lyssenko, V.* ; Weedon, M.N.* ; Knowles, J.W.* ; Alkayyali, S.* ; Assimes, T.L.* ; Quertermous, T.* ; Abbasi, F.* ; Paananen, J.* ; Häring, H.-U. ; Hansen, T.* ; Pedersen, O.* ; Smith, U.* ; Laakso, M.* ; MAGIC Investigators (Gieger, C. ; Wichmann, H.-E. ; Grallert, H. ; Thorand, B. ; Illig, T. ; Meisinger, C.) ; DIAGRAM Consortium (Huth, C. ; Grallert, H. ; Meitinger, T. ; Gieger, C. ; Wichmann, H.-E. ; Illig, T. ; Thorand, B. ; Petersen, A.-K. ; Klopp, N.) ; Dekker, J.M.* ; Nolan, J.J.* ; Groop, L.* ; Ferrannini, E.* ; Adam, K.-P.* ; Gall, W.E.* ; Frayling, T.M.* ; Walker, M.*

Genetic variants associated with glycine metabolism and their role in insulin sensitivity and type 2 diabetes.

Diabetes 62, 2141-2150 (2013)
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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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
ISSN (print) / ISBN 0012-1797
e-ISSN 1939-327X
Journal Diabetes
Quellenangaben Volume: 62, Issue: 6, Pages: 2141-2150 Article Number: , Supplement: ,
Publisher American Diabetes Association
Publishing Place Alexandria, VA.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Research Unit Molecular Epidemiology (AME)
Institute of Epidemiology II (EPI2)
CCG Biomarker for the subclassification of T2DM (KKG-KDB)
Institute of Genetic Epidemiology (IGE)
Institute of Human Genetics (IHG)
Institute of Epidemiology (EPI)
Institute of Diabetes Research and Metabolic Diseases (IDM)