Polymorphisms within Novel Risk Loci for Type 2 Diabetes Determine β-Cell Function
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{"title"=>"Polymorphisms within novel risk loci for type 2 diabetes determine β-cell function", "type"=>"journal", "authors"=>[{"first_name"=>"Harald", "last_name"=>"Staiger", "scopus_author_id"=>"6603742406"}, {"first_name"=>"Fausto", "last_name"=>"Machicao", "scopus_author_id"=>"26643593000"}, {"first_name"=>"Norbert", "last_name"=>"Stefan", "scopus_author_id"=>"7004234469"}, {"first_name"=>"Otto", "last_name"=>"Tschritter", "scopus_author_id"=>"6602108194"}, {"first_name"=>"Claus", "last_name"=>"Thamer", "scopus_author_id"=>"6602830831"}, {"first_name"=>"Konstantinos", "last_name"=>"Kantartzis", "scopus_author_id"=>"12769100600"}, {"first_name"=>"Silke A.", "last_name"=>"Schäfer", "scopus_author_id"=>"14056754200"}, {"first_name"=>"Kerstin", "last_name"=>"Kirchhoff", "scopus_author_id"=>"23982515500"}, {"first_name"=>"Andreas", "last_name"=>"Fritsche", "scopus_author_id"=>"7005146968"}, {"first_name"=>"Hans Ulrich", "last_name"=>"Häring", "scopus_author_id"=>"36038728300"}], "year"=>2007, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-38849129636", "pui"=>"351420086", "doi"=>"10.1371/journal.pone.0000832", "sgr"=>"38849129636", "pmid"=>"17786204"}, "id"=>"65846eda-ff42-3ab2-8fe5-f1294f586e9c", "abstract"=>"BACKGROUND Type 2 diabetes arises when insulin resistance-induced compensatory insulin secretion exhausts. Insulin resistance and/or beta-cell dysfunction result from the interaction of environmental factors (high-caloric diet and reduced physical activity) with a predisposing polygenic background. Very recently, genetic variations within four novel genetic loci (SLC30A8, HHEX, EXT2, and LOC387761) were reported to be more frequent in subjects with type 2 diabetes than in healthy controls. However, associations of these variations with insulin resistance and/or beta-cell dysfunction were not assessed. METHODOLOGY/PRINCIPAL FINDINGS By genotyping of 921 metabolically characterized German subjects for the reported candidate single nucleotide polymorphisms (SNPs), we show that the major alleles of the SLC30A8 SNP rs13266634 and the HHEX SNP rs7923837 associate with reduced insulin secretion stimulated by orally or intravenously administered glucose, but not with insulin resistance. In contrast, the other reported type 2 diabetes candidate SNPs within the EXT2 and LOC387761 loci did not associate with insulin resistance or beta-cell dysfunction, respectively. CONCLUSIONS/SIGNIFICANCE The HHEX and SLC30A8 genes encode for proteins that were shown to be required for organogenesis of the ventral pancreas and for insulin maturation/storage, respectively. Therefore, the major alleles of type 2 diabetes candidate SNPs within these genetic loci represent crucial alleles for beta-cell dysfunction and, thus, might confer increased susceptibility of beta-cells towards adverse environmental factors.", "link"=>"http://www.mendeley.com/research/polymorphisms-within-novel-risk-loci-type-2-diabetes-determine-%CE%B2cell-function", "reader_count"=>2, "reader_count_by_academic_status"=>{"Student > Bachelor"=>1, "Lecturer"=>1}, "reader_count_by_user_role"=>{"Student > Bachelor"=>1, "Lecturer"=>1}, "reader_count_by_subject_area"=>{"Medicine and Dentistry"=>1, "Sports and Recreations"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Sports and Recreations"=>{"Sports and Recreations"=>1}}, "group_count"=>0}

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Figshare

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  • {"files"=>["https://ndownloader.figshare.com/files/946067"], "description"=>"<p>Clinical characteristics of the study population (N = 921).</p>", "links"=>[], "tags"=>["diabetes and endocrinology", "genetics and genomics/genetics of disease", "diabetes and endocrinology/type 2 diabetes"], "article_id"=>616428, "categories"=>["Chemistry", "Virology", "Genetics"], "users"=>["Harald Staiger", "Fausto Machicao", "Norbert Stefan", "Otto Tschritter", "Claus Thamer", "Konstantinos Kantartzis", "Silke A. Schäfer", "Kerstin Kirchhoff", "Andreas Fritsche", "Hans-Ulrich Häring"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0000832.t001", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Clinical_characteristics_of_the_study_population_N_8202_8202_921_/616428", "title"=>"Clinical characteristics of the study population (N = 921).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-21 12:02:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/946121"], "description"=>"<p>For statistical analysis, data were log-transformed. Plasma glucose levels and indices of insulin sensitivity were adjusted for gender, age, and BMI. Indices of insulin secretion were adjusted for gender, age, BMI, and ISI (OGTT). p<sub>1</sub> – unadjusted; p<sub>2</sub> – adjusted, additive model; p<sub>3</sub> – adjusted, dominant model. AUC – area under the curve; HOMA-IR – homeostasis model assessment of insulin resistance; ISI – insulin sensitivity index; MAF – minor allele frequency; SNP – single nucleotide polymorphism. *subgroup (N = 491).</p>", "links"=>[], "tags"=>["snps", "rs1111875", "rs7923837", "insulin"], "article_id"=>616474, "categories"=>["Chemistry", "Virology", "Genetics"], "users"=>["Harald Staiger", "Fausto Machicao", "Norbert Stefan", "Otto Tschritter", "Claus Thamer", "Konstantinos Kantartzis", "Silke A. Schäfer", "Kerstin Kirchhoff", "Andreas Fritsche", "Hans-Ulrich Häring"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0000832.t003", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Correlations_of_HHEX_SNPs_rs1111875_and_rs7923837_with_insulin_sensitivity_and_insulin_secretion_/616474", "title"=>"Correlations of <i>HHEX</i> SNPs rs1111875 and rs7923837 with insulin sensitivity and insulin secretion.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-21 12:02:37"}

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Relative Metric

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