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Common genetic dete...
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Kelliny, Clara
(författare)
Common genetic determinants of glucose homeostasis in healthy children : the European youth heart study
- Artikel/kapitelEngelska2009
Förlag, utgivningsår, omfång ...
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2009-09-09
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American Diabetes Association,2009
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printrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:oru-19133
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https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-19133URI
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https://doi.org/10.2337/db09-0374DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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OBJECTIVE-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. RESEARCH DESIGN AND METHODS-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). RESULTS-Strongest associations were observed for G6PC2 and MTNR1B, with mean fasting glucose levels (95% Cl) 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 P-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. CONCLUSIONS-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. Diabetes 58:2939-2945, 2009
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Biuppslag (personer, institutioner, konferenser, titlar ...)
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Ekelund, UlfÖrebro universitet,Hälsoakademin(Swepub:oru)ued
(författare)
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Andersen, Lars Bo
(författare)
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Brage, Sören
(författare)
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Loos, Ruth J. F.
(författare)
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Wareham, Nicholas J.
(författare)
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Langenberg, Claudia
(författare)
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Örebro universitetHälsoakademin
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Diabetes: American Diabetes Association58:12, s. 2939-29450012-17971939-327X
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