We are analyzing https://link.springer.com/article/10.1007/s00109-010-0687-1.

Title:
Genetic variation within the NR1H2 gene encoding liver X receptor β associates with insulin secretion in subjects at increased risk for type 2 diabetes | Journal of Molecular Medicine
Description:
The liver X receptors (LXRs)-α and -β play a crucial role in control of insulin production and secretion in pancreatic β-cells. We hypothesized that common variants in the NR1H2 and NR1H3 genes, encoding LXR-β and -α, respectively, may alter pancreatic β-cell function. One thousand five hundred seventy-four subjects of European ancestry with elevated risk for type 2 diabetes were genotyped for the two NR1H2 single nucleotide polymorphisms (SNPs) rs2248949 and rs1405655 and for the four NR1H3 SNPs rs11039149, rs3758673, rs12221497 and rs2279238, and association studies with metabolic traits were performed. Metabolic characterization comprised an oral glucose tolerance test (OGTT) in all participants and, in addition, a hyperinsulinemic–euglycemic clamp and an intravenous glucose tolerance test (IVGTT) in subsets. One hundred per cent of common genetic variation (minor allele frequency ≥1%) within the NR1H2 and NR1H3 loci (D′ = 1.0; r² ≥ 0.8) were covered by the six chosen tagging SNPs. NR1H2 rs2248949 was nominally associated with OGTT-derived first-phase insulin secretion and proinsulin conversion to insulin and significantly associated with the AUC of insulin levels during the IVGTT (p = 0.007) after adjustment for age, gender, BMI and insulin sensitivity in the dominant model, with the minor allele conferring reduced pancreatic β-cell function to the carriers. In subjects of European ancestry at increased risk for type 2 diabetes, common variation within the NR1H2 gene impaired insulin secretion, which may facilitate the development of type 2 diabetes.
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Keywords {🔍}

article, diabetes, google, scholar, pubmed, cas, type, insulin, liver, receptor, glucose, nrh, association, loci, research, genetic, secretion, risk, pancreatic, genomewide, genet, subjects, access, susceptibility, nat, privacy, cookies, function, content, data, journal, variation, gene, ketterer, müssig, machicao, stefan, fritsche, hansulrich, häring, tolerance, study, activation, tübingen, european, information, publish, search, encoding, caroline,

Topics {✒️}

large-scale association analysis hans-ulrich häring month download article/chapter genome-wide association signals death domain protein genome-wide association study genome-wide association studies genome-wide association data beta cell function beta-cell function full article pdf pancreatic beta-cells pancreatic β-cells genetic loci implicated encoding lxr-β privacy choices/manage cookies cell cycle arrest phase insulin secretion receptor β associates german research foundation metabolic characterization comprised oral glucose challenge steffensen kr peripheral insulin sensitivity german federal ministry molecular medicine aims receptors van duijn cm population-based study receptor agonist mediated receptor-mediated lipotoxicity early childhood diabetes related subjects article ketterer fasting glucose homeostasis hyperinsulinemic–euglycemic clamp de bakker pi ob/ob mice international hapmap project international hapmap consortium excellent technical assistance otfried-müller-str electronic supplementary material conditions privacy policy article journal european economic area german center article log florez jc putative metabolic effects

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         description:The liver X receptors (LXRs)-α and -β play a crucial role in control of insulin production and secretion in pancreatic β-cells. We hypothesized that common variants in the NR1H2 and NR1H3 genes, encoding LXR-β and -α, respectively, may alter pancreatic β-cell function. One thousand five hundred seventy-four subjects of European ancestry with elevated risk for type 2 diabetes were genotyped for the two NR1H2 single nucleotide polymorphisms (SNPs) rs2248949 and rs1405655 and for the four NR1H3 SNPs rs11039149, rs3758673, rs12221497 and rs2279238, and association studies with metabolic traits were performed. Metabolic characterization comprised an oral glucose tolerance test (OGTT) in all participants and, in addition, a hyperinsulinemic–euglycemic clamp and an intravenous glucose tolerance test (IVGTT) in subsets. One hundred per cent of common genetic variation (minor allele frequency ≥1%) within the NR1H2 and NR1H3 loci (D′ = 1.0; r² ≥ 0.8) were covered by the six chosen tagging SNPs. NR1H2 rs2248949 was nominally associated with OGTT-derived first-phase insulin secretion and proinsulin conversion to insulin and significantly associated with the AUC of insulin levels during the IVGTT (p = 0.007) after adjustment for age, gender, BMI and insulin sensitivity in the dominant model, with the minor allele conferring reduced pancreatic β-cell function to the carriers. In subjects of European ancestry at increased risk for type 2 diabetes, common variation within the NR1H2 gene impaired insulin secretion, which may facilitate the development of type 2 diabetes.
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      headline:Genetic variation within the NR1H2 gene encoding liver X receptor β associates with insulin secretion in subjects at increased risk for type 2 diabetes
      description:The liver X receptors (LXRs)-α and -β play a crucial role in control of insulin production and secretion in pancreatic β-cells. We hypothesized that common variants in the NR1H2 and NR1H3 genes, encoding LXR-β and -α, respectively, may alter pancreatic β-cell function. One thousand five hundred seventy-four subjects of European ancestry with elevated risk for type 2 diabetes were genotyped for the two NR1H2 single nucleotide polymorphisms (SNPs) rs2248949 and rs1405655 and for the four NR1H3 SNPs rs11039149, rs3758673, rs12221497 and rs2279238, and association studies with metabolic traits were performed. Metabolic characterization comprised an oral glucose tolerance test (OGTT) in all participants and, in addition, a hyperinsulinemic–euglycemic clamp and an intravenous glucose tolerance test (IVGTT) in subsets. One hundred per cent of common genetic variation (minor allele frequency ≥1%) within the NR1H2 and NR1H3 loci (D′ = 1.0; r² ≥ 0.8) were covered by the six chosen tagging SNPs. NR1H2 rs2248949 was nominally associated with OGTT-derived first-phase insulin secretion and proinsulin conversion to insulin and significantly associated with the AUC of insulin levels during the IVGTT (p = 0.007) after adjustment for age, gender, BMI and insulin sensitivity in the dominant model, with the minor allele conferring reduced pancreatic β-cell function to the carriers. In subjects of European ancestry at increased risk for type 2 diabetes, common variation within the NR1H2 gene impaired insulin secretion, which may facilitate the development of type 2 diabetes.
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      name:German Center for Diabetes Research (DZD), Tübingen, Germany
      name:Division of Endocrinology, Diabetology, Angiology, Nephrology, and Clinical Chemistry, Department of Internal Medicine, Eberhard Karls University Tübingen, Member of the German Center for Diabetes Research (DZD), Tübingen, Germany
      name:German Center for Diabetes Research (DZD), Tübingen, Germany
      name:Division of Endocrinology, Diabetology, Angiology, Nephrology, and Clinical Chemistry, Department of Internal Medicine, Eberhard Karls University Tübingen, Member of the German Center for Diabetes Research (DZD), Tübingen, Germany
      name:German Center for Diabetes Research (DZD), Tübingen, Germany
      name:Division of Endocrinology, Diabetology, Angiology, Nephrology, and Clinical Chemistry, Department of Internal Medicine, Eberhard Karls University Tübingen, Member of the German Center for Diabetes Research (DZD), Tübingen, Germany
      name:German Center for Diabetes Research (DZD), Tübingen, Germany
      name:Division of Endocrinology, Diabetology, Angiology, Nephrology, and Clinical Chemistry, Department of Internal Medicine, Eberhard Karls University Tübingen, Member of the German Center for Diabetes Research (DZD), Tübingen, Germany
      name:German Center for Diabetes Research (DZD), Tübingen, Germany
      name:Division of Endocrinology, Diabetology, Angiology, Nephrology, and Clinical Chemistry, Department of Internal Medicine, Eberhard Karls University Tübingen, Member of the German Center for Diabetes Research (DZD), Tübingen, Germany
      name:German Center for Diabetes Research (DZD), Tübingen, Germany
      name:Medizinische Klinik IV, Universitätsklinikum Tübingen, Tübingen, Germany
      name:Division of Endocrinology, Diabetology, Angiology, Nephrology, and Clinical Chemistry, Department of Internal Medicine, Eberhard Karls University Tübingen, Member of the German Center for Diabetes Research (DZD), Tübingen, Germany
      name:German Center for Diabetes Research (DZD), Tübingen, Germany
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