Association of CDH13 Genotypes/Haplotypes with Circulating Adiponectin Levels, Metabolic Syndrome, and Related Metabolic Phenotypes: The Role of the Suppression Effect
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{"title"=>"Association of CDH13 genotypes/haplotypes with circulating adiponectin levels, metabolic syndrome, and related metabolic phenotypes: The role of the suppression effect", "type"=>"journal", "authors"=>[{"first_name"=>"Ming Sheng", "last_name"=>"Teng", "scopus_author_id"=>"7101891710"}, {"first_name"=>"Lung An", "last_name"=>"Hsu", "scopus_author_id"=>"7401644878"}, {"first_name"=>"Semon", "last_name"=>"Wu", "scopus_author_id"=>"55495117400"}, {"first_name"=>"Yu Chen", "last_name"=>"Sun", "scopus_author_id"=>"55608098400"}, {"first_name"=>"Shu Hui", "last_name"=>"Juan", "scopus_author_id"=>"26643130800"}, {"first_name"=>"Yu Lin", "last_name"=>"Ko", "scopus_author_id"=>"7401678323"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"25875811", "sgr"=>"84929993431", "doi"=>"10.1371/journal.pone.0122664", "scopus"=>"2-s2.0-84929993431", "pui"=>"604107650", "issn"=>"19326203"}, "id"=>"484cd958-1491-3180-aba0-386d56b33889", "abstract"=>"OBJECTIVE: Previous genome-wide association studies have indicated an association between CDH13 genotypes and adiponectin levels. In this study, we used mediation analysis to assess the statistical association between CDH13 locus variants and adiponectin levels, metabolic syndrome, and related metabolic phenotypes.\\n\\nMETHODS AND RESULTS: A sample population of 530 Taiwanese participants was enrolled. Four CDH13 gene variants in the promoter and intron 1 regions were genotyped. After adjustment for clinical covariates, the CDH13 genotypes/haplotypes exhibited an association with the adiponectin levels (lowest P = 1.95 × 10-11 for rs4783244 and lowest P = 3.78 × 10-13 for haplotype ATTT). Significant correlations were observed between the adiponectin levels and the various metabolic syndrome-related phenotypes (all P ≤ 0.005). After further adjustment for the adiponectin levels, participants with a minor allele of rs12051272 revealed a considerable association with a more favorable metabolic profile, including higher insulin sensitivity, high-density lipoprotein cholesterol levels, lower diastolic blood pressure, circulating levels of fasting plasma glucose, and triglycerides, and as a lower risk of metabolic syndrome (all P < 0.05). The mediation analysis further revealed a suppression effect of the adiponectin levels on the association between CDH13 genotypes and metabolic syndrome and its related phenotypes (Sobel test; all P < 0.001).\\n\\nCONCLUSION: The genetic polymorphisms at the CDH13 locus independently affect the adiponectin levels, whereas the adiponectin levels exhibit a suppressive effect on the association between CDH13 locus variants and various metabolic phenotypes and metabolic syndrome. In addition, these results provide further evidence of the association between the CDH13 gene variants and the risks of metabolic syndrome and atherosclerotic cardiovascular disease.", "link"=>"http://www.mendeley.com/research/association-cdh13-genotypeshaplotypes-circulating-adiponectin-levels-metabolic-syndrome-related-meta", "reader_count"=>8, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>2, "Researcher"=>2, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>1, "Other"=>1, "Student > Master"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>2, "Researcher"=>2, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>1, "Other"=>1, "Student > Master"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>3, "Medicine and Dentistry"=>2, "Business, Management and Accounting"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>3}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>1}}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2016386"], "description"=>"<div><p>Objective</p><p>Previous genome-wide association studies have indicated an association between <i>CDH13</i> genotypes and adiponectin levels. In this study, we used mediation analysis to assess the statistical association between <i>CDH13</i> locus variants and adiponectin levels, metabolic syndrome, and related metabolic phenotypes.</p><p>Methods and results</p><p>A sample population of 530 Taiwanese participants was enrolled. Four <i>CDH13</i> gene variants in the promoter and intron 1 regions were genotyped. After adjustment for clinical covariates, the <i>CDH13</i> genotypes/haplotypes exhibited an association with the adiponectin levels (lowest <i>P</i> = 1.95 × 10<sup>−11</sup> for rs4783244 and lowest <i>P</i> = 3.78 × 10<sup>−13</sup> for haplotype <i>ATTT</i>). Significant correlations were observed between the adiponectin levels and the various metabolic syndrome-related phenotypes (all <i>P</i> ≤ 0.005). After further adjustment for the adiponectin levels, participants with a minor allele of rs12051272 revealed a considerable association with a more favorable metabolic profile, including higher insulin sensitivity, high-density lipoprotein cholesterol levels, lower diastolic blood pressure, circulating levels of fasting plasma glucose, and triglycerides, and as a lower risk of metabolic syndrome (all <i>P</i> < 0.05). The mediation analysis further revealed a suppression effect of the adiponectin levels on the association between <i>CDH13</i> genotypes and metabolic syndrome and its related phenotypes (Sobel test; all <i>P <</i> 0.001).</p><p>Conclusion</p><p>The genetic polymorphisms at the <i>CDH13</i> locus independently affect the adiponectin levels, whereas the adiponectin levels exhibit a suppressive effect on the association between <i>CDH13</i> locus variants and various metabolic phenotypes and metabolic syndrome. In addition, these results provide further evidence of the association between the <i>CDH13</i> gene variants and the risks of metabolic syndrome and atherosclerotic cardiovascular disease.</p></div>", "links"=>[], "tags"=>["adiponectin levels", "fasting plasma glucose", "association", "CDH 13 gene variants", "intron 1 regions", "mediation analysis", "Circulating Adiponectin Levels", "ATTT", "CDH 13 genotypes", "adiponectin levels exhibit", "lipoprotein cholesterol levels", "resultsA sample population", "Related Metabolic Phenotypes", "CDH 13 locus", "syndrome", "CDH 13 locus variants", "diastolic blood pressure"], "article_id"=>1376647, "categories"=>["Uncategorised"], "users"=>["Ming-Sheng Teng", "Lung-An Hsu", "Semon Wu", "Yu-Chen Sun", "Shu-Hui Juan", "Yu-Lin Ko"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122664", "stats"=>{"downloads"=>3, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Association_of_CDH13_Genotypes_Haplotypes_with_Circulating_Adiponectin_Levels_Metabolic_Syndrome_and_Related_Metabolic_Phenotypes_The_Role_of_the_Suppression_Effect/1376647", "title"=>"Association of <i>CDH13</i> Genotypes/Haplotypes with Circulating Adiponectin Levels, Metabolic Syndrome, and Related Metabolic Phenotypes: The Role of the Suppression Effect", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-04-13 03:35:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/2016385"], "description"=>"<p><i>CDH13</i> genotypes represent rs12051272, which was analyzed in the dominant models, α: unstandardized coefficient for the association between the <i>CDH13</i> genetic variants and log adiponectin levels; β: unstandardized coefficient for the association between adiponectin and metabolic phenotypes, such as diastolic BP, glucose levels, QUICKI, HDL cholesterol, triglyceride levels and metabolic syndrome (when adjusted for the <i>CDH13</i> genetic variants). Direct effect = γ’, Total effect = αβ + γ’, Mediation (indirect) effect = αβ</p><p>BP, blood pressure; HDL, high-density lipoprotein; QUICKI, quantitative insulin sensitivity check index;</p><p>Mediation tests for adiponectin levels on the association between <i>CDH13</i> genotypes and metabolic phenotypes.</p>", "links"=>[], "tags"=>["adiponectin levels", "fasting plasma glucose", "association", "CDH 13 gene variants", "intron 1 regions", "mediation analysis", "Circulating Adiponectin Levels", "ATTT", "CDH 13 genotypes", "adiponectin levels exhibit", "lipoprotein cholesterol levels", "resultsA sample population", "Related Metabolic Phenotypes", "CDH 13 locus", "syndrome", "CDH 13 locus variants", "diastolic blood pressure"], "article_id"=>1376646, "categories"=>["Uncategorised"], "users"=>["Ming-Sheng Teng", "Lung-An Hsu", "Semon Wu", "Yu-Chen Sun", "Shu-Hui Juan", "Yu-Lin Ko"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122664.t004", "stats"=>{"downloads"=>4, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mediation_tests_for_adiponectin_levels_on_the_association_between_CDH13_genotypes_and_metabolic_phenotypes_/1376646", "title"=>"Mediation tests for adiponectin levels on the association between <i>CDH13</i> genotypes and metabolic phenotypes.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-04-13 03:35:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/2016382"], "description"=>"<p>BP, blood pressure; HDL, high-density lipoprotein; LDL, low-density lipoprotein; HOMA-IR, homeostasis model assessment of insulin resistance; QUICKI, quantitative insulin sensitivity check index; Continuous variables are presented as mean ± standard deviation (SD).</p><p>Baseline characteristics of the health examination participants.</p>", "links"=>[], "tags"=>["adiponectin levels", "fasting plasma glucose", "association", "CDH 13 gene variants", "intron 1 regions", "mediation analysis", "Circulating Adiponectin Levels", "ATTT", "CDH 13 genotypes", "adiponectin levels exhibit", "lipoprotein cholesterol levels", "resultsA sample population", "Related Metabolic Phenotypes", "CDH 13 locus", "syndrome", "CDH 13 locus variants", "diastolic blood pressure"], "article_id"=>1376643, "categories"=>["Uncategorised"], "users"=>["Ming-Sheng Teng", "Lung-An Hsu", "Semon Wu", "Yu-Chen Sun", "Shu-Hui Juan", "Yu-Lin Ko"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122664.t001", "stats"=>{"downloads"=>5, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Baseline_characteristics_of_the_health_examination_participants_/1376643", "title"=>"Baseline characteristics of the health examination participants.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-04-13 03:35:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/2016381"], "description"=>"<p>Adiponectin levels as a mediator of the association between the <i>CDH13</i> genotype and the metabolic syndrome and metabolic syndrome-related phenotypes. Linear or binary regression models were used to assess the following path associations: in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0122664#pone.0122664.g001\" target=\"_blank\">Fig 1</a> (F): (α) relationship between the <i>CDH13</i> genotype and adiponectin, (β) relationship between adiponectin and metabolic syndrome, (αβ + γ’) relationship between the <i>CDH13</i> genotype and metabolic syndrome, and (γ’) relationship between the <i>CDH13</i> genotype and metabolic syndrome after adjustment for adiponectin levels. Each estimate along the path represents the unstandardized β coefficient from the regression model. The results indicate that after adjustment for adiponectin levels, the CDH13 genotype exhibited a stronger association with the metabolic syndrome. The direct effects (γ’) of the <i>CDH13</i> genotype on the metabolic syndrome (−1.136) were greater than the total effects (αβ + γ’) (−0.492) and revealed similar magnitudes and opposite signs than those of the mediation effects (αβ) (0.541), suggesting significant mediation (suppression) by the adiponectin levels. All of the models were adjusted for age, sex, BMI, and current smoking status. °P < 0.05. In addition, the other metabolic syndrome-related phenotypes exhibited similar suppression effects (B, C, D, and E). <sup>#</sup><i>CDH13</i> genotypes: dominant inheritance model was used (<i>GG vs</i>. <i>GT + TT</i> for rs12051272).</p>", "links"=>[], "tags"=>["adiponectin levels", "fasting plasma glucose", "association", "CDH 13 gene variants", "intron 1 regions", "mediation analysis", "Circulating Adiponectin Levels", "ATTT", "CDH 13 genotypes", "adiponectin levels exhibit", "lipoprotein cholesterol levels", "resultsA sample population", "Related Metabolic Phenotypes", "CDH 13 locus", "syndrome", "CDH 13 locus variants", "diastolic blood pressure"], "article_id"=>1376642, "categories"=>["Uncategorised"], "users"=>["Ming-Sheng Teng", "Lung-An Hsu", "Semon Wu", "Yu-Chen Sun", "Shu-Hui Juan", "Yu-Lin Ko"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122664.g001", "stats"=>{"downloads"=>4, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_three_variable_mediation_model_/1376642", "title"=>"A three-variable mediation model.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-04-13 03:35:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/2016384"], "description"=>"<p>Abbreviations as in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0122664#pone.0122664.t001\" target=\"_blank\">Table 1</a></p><p>*<i>CDH13</i> genotypes: dominant inheritance model was used (<i>GG vs</i>. <i>GT + TT</i> for rs12051272).</p><p>** For metabolic syndrome, the lanes denote the odds ratios (95% confidence interval [CI]).</p><p>Association of <i>CDH13</i> rs12051272 genotypes, serum adiponectin levels and metabolic syndrome-related phenotypes.</p>", "links"=>[], "tags"=>["adiponectin levels", "fasting plasma glucose", "association", "CDH 13 gene variants", "intron 1 regions", "mediation analysis", "Circulating Adiponectin Levels", "ATTT", "CDH 13 genotypes", "adiponectin levels exhibit", "lipoprotein cholesterol levels", "resultsA sample population", "Related Metabolic Phenotypes", "CDH 13 locus", "syndrome", "CDH 13 locus variants", "diastolic blood pressure"], "article_id"=>1376645, "categories"=>["Uncategorised"], "users"=>["Ming-Sheng Teng", "Lung-An Hsu", "Semon Wu", "Yu-Chen Sun", "Shu-Hui Juan", "Yu-Lin Ko"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122664.t003", "stats"=>{"downloads"=>6, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Association_of_CDH13_rs12051272_genotypes_serum_adiponectin_levels_and_metabolic_syndrome_related_phenotypes_/1376645", "title"=>"Association of <i>CDH13</i> rs12051272 genotypes, serum adiponectin levels and metabolic syndrome-related phenotypes.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-04-13 03:35:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/2016383"], "description"=>"<p>N: number of subjects; P value, Unadjusted;</p><p>P<i>°</i>value, adjusted for age, sex, body mass index, and current smoking status.</p><p><i>CDH13</i> genotypes and adiponectin levels.</p>", "links"=>[], "tags"=>["adiponectin levels", "fasting plasma glucose", "association", "CDH 13 gene variants", "intron 1 regions", "mediation analysis", "Circulating Adiponectin Levels", "ATTT", "CDH 13 genotypes", "adiponectin levels exhibit", "lipoprotein cholesterol levels", "resultsA sample population", "Related Metabolic Phenotypes", "CDH 13 locus", "syndrome", "CDH 13 locus variants", "diastolic blood pressure"], "article_id"=>1376644, "categories"=>["Uncategorised"], "users"=>["Ming-Sheng Teng", "Lung-An Hsu", "Semon Wu", "Yu-Chen Sun", "Shu-Hui Juan", "Yu-Lin Ko"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122664.t002", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CDH13_genotypes_and_adiponectin_levels_/1376644", "title"=>"<i>CDH13</i> genotypes and adiponectin levels.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-04-13 03:35:42"}

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{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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