title: Association between copy-number variation on metabolic phenotypes and HDL-C levels in patients with polycystic ovary syndrome.
abstract: Polygenic diseases with a broad phenotypic spectrum, such as polycystic ovary syndrome (PCOS), present a particular challenge in terms of identifying the underlying genetic mechanisms, nevertheless genetic variants have impact on the individual phenotype. We aimed to determine if next to genetic variations like SNPs further mechanisms might play a role in the pathogenesis of PCOS. We examined the effect of copy-number variations (CNVs) on metabolic phenotypes in PCOS. The intragenic rs1244979, rs2815752 in NEGR1 gene, and rs780094 in GCKR gene were genotyped and CNVs were determined by droplet digital polymerase chain reaction (ddPCR) in PCOS patients (n = 153) and controls without metabolic syndrome (n = 142). The study indicated that SNPs are not associated with the pathogenesis of PCOS but affect metabolic phenotypes. The CNVs investigated show a lower variability in PCOS than in CON. Furthermore, we provided direct evidence that the copy number, but not the genotype of the CNV in the genomic regions of rs780094(GCKR) is associated with low level of high-density lipoprotein cholesterol in PCOS. This study supports the hypothesis that not only genetic variants, but also CNVs in metabolically relevant genes, have an effect on metabolic phenotypes in our group of PCOS patients.
authors.affiliation: Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center at the Heinrich-Heine-University Düsseldorf, Leibniz Center for Diabetes Research, 40225, Düsseldorf, Germany. bknebel@ddz.uni-dusseldorf.de.|German Center of Diabetes Research Partner, Duesseldorf, Germany. bknebel@ddz.uni-dusseldorf.de.
authors.forename: Birgit
authors.initials: B
authors.lastname: Knebel
authors.affiliation: Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center at the Heinrich-Heine-University Düsseldorf, Leibniz Center for Diabetes Research, 40225, Düsseldorf, Germany.|German Center of Diabetes Research Partner, Duesseldorf, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Lehr
authors.affiliation: Endokrinologikum Hamburg, 22767, Hamburg, Germany.
authors.forename: Onno E
authors.initials: OE
authors.lastname: Janssen
authors.affiliation: MVZ Limbach Wuppertal, 2349, Wuppertal, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Hahn
authors.affiliation: Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center at the Heinrich-Heine-University Düsseldorf, Leibniz Center for Diabetes Research, 40225, Düsseldorf, Germany.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Jacob
authors.affiliation: Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center at the Heinrich-Heine-University Düsseldorf, Leibniz Center for Diabetes Research, 40225, Düsseldorf, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Nitzgen
authors.affiliation: Department of Internal Medicine I, University Hospital Aachen, 52074, Aachen, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Müller-Wieland
authors.affiliation: Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center at the Heinrich-Heine-University Düsseldorf, Leibniz Center for Diabetes Research, 40225, Düsseldorf, Germany.|German Center of Diabetes Research Partner, Duesseldorf, Germany.
authors.forename: Jorg
authors.initials: J
authors.lastname: Kotzka
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D015519:Bone Density; D016022:Case-Control Studies; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D008076:Cholesterol, HDL / Q000378:metabolism*; D056915:DNA Copy Number Variations; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D024821:Metabolic Syndrome / Q000235:genetics*; D008875:Middle Aged; D011085:Polycystic Ovary Syndrome / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015816:Cell Adhesion Molecules, Neuronal; D008076:Cholesterol, HDL; C485100:GCKR protein, human; D058851:GPI-Linked Proteins; C485559:NEGR1 protein, human
keywords: Copy-number variation; DdPCR; Droplet digital polymerase chain reaction; Metabolic syndrome; Polycystic ovary syndrome (PCOS)