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- Title
Common genetic determinants of glucose homeostasis in healthy children: the European Youth Heart Study.
- Authors
Kelliny C; Ekelund U; Andersen LB; Brage S; Loos RJ; Wareham NJ; Langenberg C; Kelliny, Clara; Ekelund, Ulf; Andersen, Lars Bo; Brage, Soren; Loos, Ruth J F; Wareham, Nicholas J; Langenberg, Claudia
- Abstract
<bold>Objective: </bold>The goal of this study was to investigate whether the effects of common genetic variants associated with fasting glucose in adults are detectable in healthy children.<bold>Research Design and Methods: </bold>Single nucleotide polymorphisms in MTNR1B (rs10830963), G6PC2 (rs560887), and GCK (rs4607517) were genotyped in 2,025 healthy European children aged 9-11 and 14-16 years. Associations with fasting glucose, insulin, homeostasis model assessment (HOMA)-insulin resistance (IR) and HOMA-B were investigated along with those observed for type 2 diabetes variants available in this study (CDKN2A/B, IGF2BP2, CDKAL1, SLC30A8, HHEX-IDE, and Chr 11p12).<bold>Results: </bold>Strongest associations were observed for G6PC2 and MTNR1B, with mean fasting glucose levels (95% CI) being 0.084 (0.06-0.11) mmol/l, P = 7.9 x 10(-11) and 0.069 (0.04-0.09) mmol/l, P = 1.9 x 10(-7) higher per risk allele copy, respectively. A similar but weaker trend was observed for GCK (0.028 [-0.006 to 0.06] mmol/l, P = 0.11). All three variants were associated with lower beta-cell function (HOMA-B P = 9.38 x 10(-5), 0.004, and 0.04, respectively). SLC30A8 (rs13266634) was the only type 2 diabetes variant associated with higher fasting glucose (0.033 mmol/l [0.01-0.06], P = 0.01). Calculating a genetic predisposition score adding the number of risk alleles of G6PC2, MTNR1B, GCK, and SLC30A8 showed that glucose levels were successively higher in children carrying a greater number of risk alleles (P = 7.1 x 10(-17)), with mean levels of 5.34 versus 4.91 mmol/l comparing children with seven alleles (0.6% of all children) to those with none (0.5%). No associations were found for fasting insulin or HOMA-IR with any of the variants.<bold>Conclusions: </bold>The effects of common polymorphisms influencing fasting glucose are apparent in healthy children, whereas the presence of multiple risk alleles amounts to a difference of >1 SD of fasting glucose.
- Publication
Diabetes, 2009, Vol 58, Issue 12, p2939
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db09-0374