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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{"title"=>"Variant near ADAMTS9 known to associate with type 2 diabetes is related to insulin resistance in offspring of type 2 diabetes patients - EUGENE2 study", "type"=>"journal", "authors"=>[{"first_name"=>"Trine Welløv", "last_name"=>"Boesgaard", "scopus_author_id"=>"16686109200"}, {"first_name"=>"Anette Prior", "last_name"=>"Gjesing", "scopus_author_id"=>"6507800856"}, {"first_name"=>"Niels", "last_name"=>"Grarup", "scopus_author_id"=>"15759864800"}, {"first_name"=>"Jarno", "last_name"=>"Rutanen", "scopus_author_id"=>"16064478000"}, {"first_name"=>"Per Anders", "last_name"=>"Jansson", "scopus_author_id"=>"7102211418"}, {"first_name"=>"Marta Letizia", "last_name"=>"Hribal", "scopus_author_id"=>"6603170340"}, {"first_name"=>"Giorgia", "last_name"=>"Sesti", "scopus_author_id"=>"7004528002"}, {"first_name"=>"Andreas", "last_name"=>"Fritsche", "scopus_author_id"=>"7005146968"}, {"first_name"=>"Norbert", "last_name"=>"Stefan", "scopus_author_id"=>"7004234469"}, {"first_name"=>"Harald", "last_name"=>"Staiger", "scopus_author_id"=>"6603742406"}, {"first_name"=>"Hans", "last_name"=>"Häring", "scopus_author_id"=>"36038728300"}, {"first_name"=>"Ulf", "last_name"=>"Smith", "scopus_author_id"=>"7103181011"}, {"first_name"=>"Markku", "last_name"=>"Laakso", "scopus_author_id"=>"36078643000"}, {"first_name"=>"Oluf", "last_name"=>"Pedersen", "scopus_author_id"=>"35373396900"}, {"first_name"=>"Torben", "last_name"=>"Hansen", "scopus_author_id"=>"7401667966"}], "year"=>2009, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-70349833653", "pui"=>"355396893", "doi"=>"10.1371/journal.pone.0007236", "isbn"=>"1932-6203 (Electronic)\\n1932-6203 (Linking)", "sgr"=>"70349833653", "pmid"=>"19789630"}, "id"=>"9f86f98b-1843-3243-9fd0-44512f3b8135", "abstract"=>"BACKGROUND: 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.\\n\\nMETHODOLOGY/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.\\n\\nCONCLUSION: 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.", "link"=>"http://www.mendeley.com/research/variant-near-adamts9-known-associate-type-2-diabetes-related-insulin-resistance-offspring-type-2-dia", "reader_count"=>7, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Ph. D. Student"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Ph. D. Student"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>1, "Medicine and Dentistry"=>1, "Chemistry"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Chemistry"=>{"Chemistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>2}}, "group_count"=>1}

Scopus | Further Information

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  • {"files"=>["https://ndownloader.figshare.com/files/881648"], "description"=>"<p>A) M value; B) Disposition Index; C) 1<sup>st</sup> phase insulin secretion and D) 2<sup>nd</sup> phase insulin secretion. The black diamonds represent the combined and weight (using the DerSimonian-Laird method) effects of the studies. The grey diamonds represent the combined and weight (using inverse variance) effects of the studies.</p>", "links"=>[], "tags"=>["diabetes-associated", "c-allele", "rs4607103", "transformed", "adjusted", "variants"], "article_id"=>552080, "categories"=>["Genetics"], "users"=>["Trine Welløv Boesgaard", "Anette Prior Gjesing", "Niels Grarup", "Jarno Rutanen", "Per-Anders Jansson", "Marta Letizia Hribal", "Giorgio Sesti", "Andreas Fritsche", "Norbert Stefan", "Harald Staiger", "Hans Häring", "Ulf Smith", "Markku Laakso", "Oluf Pedersen", "Torben Hansen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007236.g001", "stats"=>{"downloads"=>0, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Estimates_of_effects_for_the_diabetes_associated_major_C_allele_of_rs4607103_near_ADAMTS9_based_on_log_transformed_traits_and_adjusted_for_sex_age_and_BMI_of_the_variants_with_95_confidence_/552080", "title"=>"Estimates of effects for the diabetes-associated major C-allele of rs4607103 near <i>ADAMTS9</i> (based on log transformed traits and adjusted for sex, age and BMI) of the variants with 95% confidence.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-09-30 00:34:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/881745"], "description"=>"<p>Risk allele is denoted in bold. Data are mean±standard deviation. Unadjusted values of serum insulin and derived indices were logarithmically transformed by log10 before statistical analysis. <i>P</i>-values were calculated assuming an additive model adjusted for age and sex (BMI and waist), or age, sex, and BMI (all other traits). Indices of insulin release, M value and disposition index were calculated as described in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007236#s2\" target=\"_blank\">Methods</a>.</p>", "links"=>[], "tags"=>["metabolic-characteristics", "819", "non-diabetic", "offspring", "stratified", "genotype"], "article_id"=>552180, "categories"=>["Genetics"], "users"=>["Trine Welløv Boesgaard", "Anette Prior Gjesing", "Niels Grarup", "Jarno Rutanen", "Per-Anders Jansson", "Marta Letizia Hribal", "Giorgio Sesti", "Andreas Fritsche", "Norbert Stefan", "Harald Staiger", "Hans Häring", "Ulf Smith", "Markku Laakso", "Oluf Pedersen", "Torben Hansen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007236.t001", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Quantitative_and_metabolic_characteristics_of_819_non_diabetic_offspring_stratified_according_to_the_genotype_of_ADAMTS9_rs4607103_/552180", "title"=>"Quantitative- and metabolic-characteristics of 819 non-diabetic offspring stratified according to the genotype of <i>ADAMTS9</i> rs4607103.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-09-30 00:36:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/881803"], "description"=>"<p>Risk allele is denoted in bold. Data are mean±standard deviation. Unadjusted values of serum insulin and derived indices were logarithmically transformed by log10 before statistical analysis. <i>P</i>-values were calculated assuming an additive model adjusted for age and sex (BMI and waist), or age, sex, and BMI (all other traits). Indices of insulin release, M value and disposition index were calculated as described in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007236#s2\" target=\"_blank\">Methods</a>.</p>", "links"=>[], "tags"=>["metabolic-characteristics", "820", "non-diabetic", "offspring", "stratified", "genotype"], "article_id"=>552233, "categories"=>["Genetics"], "users"=>["Trine Welløv Boesgaard", "Anette Prior Gjesing", "Niels Grarup", "Jarno Rutanen", "Per-Anders Jansson", "Marta Letizia Hribal", "Giorgio Sesti", "Andreas Fritsche", "Norbert Stefan", "Harald Staiger", "Hans Häring", "Ulf Smith", "Markku Laakso", "Oluf Pedersen", "Torben Hansen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007236.t002", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Quantitative_and_metabolic_characteristics_of_820_non_diabetic_offspring_of_type_2_diabetes_patients_stratified_according_to_genotype_of_JAZF1_rs864745_/552233", "title"=>"Quantitative- and metabolic-characteristics of 820 non-diabetic offspring of type 2 diabetes patients, stratified according to genotype of <i>JAZF1</i> rs864745.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-09-30 00:37:13"}
  • {"files"=>["https://ndownloader.figshare.com/files/437024", "https://ndownloader.figshare.com/files/437038", "https://ndownloader.figshare.com/files/437047", "https://ndownloader.figshare.com/files/437054", "https://ndownloader.figshare.com/files/437069", "https://ndownloader.figshare.com/files/437085"], "description"=>"<div><h3>Backround</h3><p>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 <em>JAZF1</em> (rs864745), <em>THADA</em> (rs7578597), <em>TSPAN8</em> (rs7961581), <em>ADAMTS9</em> (rs4607103), <em>NOTCH2</em> (rs10923931) and the <em>CDC123/CAMK1D</em> (rs12779790) genes for associations with measures of pancreatic beta-cell function and insulin sensitivity.</p><h3>Methodology/Results</h3><p>Oral and intravenous glucose stimulated insulin release (<em>n</em> = 849) and insulin sensitivity (<em>n</em> = 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 <em>ADAMTS9</em> associated with reduced insulin-stimulated glucose uptake (<em>p</em> = 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 (<em>p</em> = 0.003 and <em>p</em> = 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 (<em>p</em> = 0.003) and increased insulin release (<em>p</em> = 0.002). The major T-allele of the intronic <em>JAZF1</em> rs864745 conferring increased diabetes risk was associated with increased 2<sup>nd</sup> phase serum insulin release during an IVGTT (<em>p</em> = 0.03), and an increased fasting serum insulin level (<em>p</em> = 0.001). The remaining variants did not show any associations with insulin response, insulin sensitivity or any other measured quantitative traits.</p><h3>Conclusion</h3><p>The present studies suggest that the diabetogenic impact of the C-allele of rs4607103 near <em>ADAMTS9</em> may in part be mediated through decreased insulin sensitivity of peripheral tissues.</p></div>", "links"=>[], "tags"=>["variant", "adamts9", "insulin", "offspring"], "article_id"=>146170, "categories"=>["Genetics"], "users"=>["Trine Welløv Boesgaard", "Anette Prior Gjesing", "Niels Grarup", "Jarno Rutanen", "Per-Anders Jansson", "Marta Letizia Hribal", "Giorgio Sesti", "Andreas Fritsche", "Norbert Stefan", "Harald Staiger", "Hans Häring", "Ulf Smith", "Markku Laakso", "Oluf Pedersen", "Torben Hansen"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0007236.s001", "https://dx.doi.org/10.1371/journal.pone.0007236.s002", "https://dx.doi.org/10.1371/journal.pone.0007236.s003", "https://dx.doi.org/10.1371/journal.pone.0007236.s004", "https://dx.doi.org/10.1371/journal.pone.0007236.s005", "https://dx.doi.org/10.1371/journal.pone.0007236.s006"], "stats"=>{"downloads"=>31, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Variant_near_ADAMTS9_Known_to_Associate_with_Type_2_Diabetes_Is_Related_to_Insulin_Resistance_in_Offspring_of_Type_2_Diabetes_Patients_EUGENE2_Study/146170", "title"=>"Variant near ADAMTS9 Known to Associate with Type 2 Diabetes Is Related to Insulin Resistance in Offspring of Type 2 Diabetes Patients—EUGENE2 Study", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2009-09-30 01:42:50"}

PMC Usage Stats | Further Information

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