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Variant near ADAMTS...
Variant near ADAMTS9 known to associate with type 2 diabetes is related to insulin resistance in offspring of type 2 diabetes patients--EUGENE2 study
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Boesgaard, T. W. (författare)
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Gjesing, A. P. (författare)
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Grarup, N. (författare)
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Rutanen, J. (författare)
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- Jansson, Per-Anders, 1961 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
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Hribal, M. L. (författare)
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Sesti, G. (författare)
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Fritsche, A. (författare)
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Stefan, N. (författare)
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Staiger, H. (författare)
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Haring, H. (författare)
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- Smith, Ulf, 1943 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
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Laakso, M. (författare)
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Pedersen, O. (författare)
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Hansen, T. (författare)
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(creator_code:org_t)
- 2009
- 2009
- Engelska.
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Ingår i: PLoS One. - 1932-6203. ; 4:9
- Relaterad länk:
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https://gup.ub.gu.se...
Abstract
Ämnesord
Stäng
- BACKROUND: A meta-analysis combining results from three genome-wide association studies and followed by large-scale replication identified six novel type 2 diabetes loci. Subsequent studies of the effect of these variants on estimates of the beta-cell function and insulin sensitivity have been inconclusive. We examined these variants located in or near the JAZF1 (rs864745), THADA (rs7578597), TSPAN8 (rs7961581), ADAMTS9 (rs4607103), NOTCH2 (rs10923931) and the CDC123/CAMK1D (rs12779790) genes for associations with measures of pancreatic beta-cell function and insulin sensitivity. METHODOLOGY/RESULTS: Oral and intravenous glucose stimulated insulin release (n = 849) and insulin sensitivity (n = 596) estimated from a hyperinsulinemic euglycemic clamp were measured in non-diabetic offspring of type 2 diabetic patients from five European populations. Assuming an additive genetic model the diabetes-associated major C-allele of rs4607103 near ADAMTS9 associated with reduced insulin-stimulated glucose uptake (p = 0.002) during a hyperinsulinemic euglycemic clamp. However, following intravenous and oral administration of glucose serum insulin release was increased in individuals with the C-allele (p = 0.003 and p = 0.01, respectively). A meta-analyse combining clamp and IVGTT data from a total of 905 non-diabetic individuals showed that the C-risk allele associated with decreased insulin sensitivity (p = 0.003) and increased insulin release (p = 0.002). The major T-allele of the intronic JAZF1 rs864745 conferring increased diabetes risk was associated with increased 2(nd) phase serum insulin release during an IVGTT (p = 0.03), and an increased fasting serum insulin level (p = 0.001). The remaining variants did not show any associations with insulin response, insulin sensitivity or any other measured quantitative traits. CONCLUSION: The present studies suggest that the diabetogenic impact of the C-allele of rs4607103 near ADAMTS9 may in part be mediated through decreased insulin sensitivity of peripheral tissues.
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Hitta via bibliotek
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PLoS One
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Till lärosätets databas
- Av författaren/redakt...
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Boesgaard, T. W.
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Gjesing, A. P.
-
Grarup, N.
-
Rutanen, J.
-
Jansson, Per-And ...
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Hribal, M. L.
-
visa fler...
-
Sesti, G.
-
Fritsche, A.
-
Stefan, N.
-
Staiger, H.
-
Haring, H.
-
Smith, Ulf, 1943
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Laakso, M.
-
Pedersen, O.
-
Hansen, T.
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visa färre...
- Artiklar i publikationen
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PLoS One
- Av lärosätet
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Göteborgs universitet