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DOI: 10.1055/s-0029-1222564
© Georg Thieme Verlag KG Stuttgart · New York
Kombinierte Analyse von Paraoxonase-1- und IGF-2-Polymorphismen bei polyzystischem Ovarsyndrom
Combined analyses of paraoxonase-1 and IGF-2 polymorphism in polycystic ovary syndromePublication History
eingereicht: 12.2.2009
akzeptiert: 24.4.2009
Publication Date:
06 May 2009 (online)

Zusammenfassung
Hintergrund: Patientinnen mit polyzystischem Ovarsyndrom (PCOS) weisen neben Reproduktionsstörungen Symptome des metabolischen Syndroms auf. Eine genetische Komponente bei PCOS ist wegen der familiären Häufung des Syndroms wahrscheinlich. Potentielle Kandidaten hierfür sind das Paraoxonase(PON)-1-Gen und der IGF–2-INS1/VTR-IGF-Cluster, deren genetische Kopplung mit dem Lipidstoffwechsel oder der Insulinsensitivität, also zentralen Aspekten auch des PCOS-Phänotyps, gezeigt wurde.
Patienten und Methodik: Der ApaI-Polymorphismus (rs:680) im IGF-2-Cluster und der –108-Polymorphismus (rs:705 379) im PON-1-Gen wurde bei 153 Patientinnen mit PCOS und bei 178 nach Alter und Body-Mass-Index angepassten Kontrollen auf eine Assoziation zu PCOS evaluiert.
Ergebnisse: Der Polymorphismus im IGF-2-Cluster wurde bei PCOS-Patientinnen und Kontrollen in vergleichbarer Frequenz (PCOS/Kontrollen: A: 0,351/0,325; G: 0,648/0,674; Odds Ratio [OR]: 0,8886, 95 %-Konfidenzintervall [95 %CI] 0,648–1,2236) und gleicher Genotypverteilung (PCOS/Kontrollen: GG: 0,399/0,461; AG: 0,4962/0,4277; AA: 0,1042/0,111) gefunden. Die Frequenz des PON-1-Polymorphismus war ebenfalls vergleichbar (PCOS/Kontrollen: T: 0,493/0,483; C: 0,5633/0,5168; OR: 0,9569, CI 95 %: 0,707–1,43024, allerdings war die Genotypverteilung (PCOS/Kontrollen: CC: 0,2679/0,2032; CT: 0,4768/0,628; TT: 0,258/0,169) signifikant verschieden. Die kombinierte Analyse beider Polymorphismen ergab, dass der Genotyp IGF-2 (GG)/ PON-1 (TT) mit einer OR von 1,64741 (0,7388 – 3,6735) sowie der Genotyp IGF-2 (AA)/ PON-1 (TT) mit einer OR von 2,6733 (0,7579 – 9,4291) bei Patientinnen mit PCOS deutlich häufiger vertreten war. Der Genotyp IGF–2 (AA)/ PON-1 (CC) konnte bei PCOS nicht identifiziert werden. Entsprechend der molekularen Analyse wurden bei den klinisch-chemischen Parametern signifikante Unterschiede identifiziert.
Folgerung: Die vorliegende Studie weist darauf hin, dass beim polyzystischen Ovarsyndrom (PCOS) erst die kombinierte Analyse potentieller Kandidatengene eine Genotyp-Phänotyp-Korrelation aufzeigen kann.
Summary
Background: Apart from impaired reproductive function patients with polycystic ovary syndrome (PCOS) also have signs and symptoms belonging to the metabolic syndrome. A genetic basis for PCOS is likely as the syndrome clusters in families. Putative candidate genes are paraoxonase (PON)-1 gene and the IGF-2 INS1/VTR IGF cluster, which have been shown to be genetically linked to lipid metabolism o insulin sensitivity, two major aspects of the PCOS phenotype.
Patients and methods: The ApaI polymorphism (rs:680) in the IGF-2 cluster and the –108 polymorphism (rs:705 379) in PON-1 were evaluated in a collective of 153 PCOS patients and 178 age and BMI matched controls for an association to PCOS.
Results: The polymorphism in the IGF-2 cluster was identified in both groups in comparable frequencies (PCOS/control: A: 0.351/0.325; G: 0.648/0.674; OR: 0.8886, 95 %CI 0,648–1.2236) and equal genotype distribution (PCOS/control: GG: 0.399/0.461; AG: 0.4962/0.4277; AA: 0.1042/0.111). Frequencies of the PON-1 polymorphism were also comparable (PCOS/control: T: 0.493/0.483; C: 0.5633/0.5168; OR: 0.9569 95 % CI: 0.707–1.43024), but the distribution (PCOS/control: CC: 0.2679/0.2032; CT: 0.4768/0.628; TT: 0.258/0.169) was significantly different. The combined analyses of both polymorphism revealed that the genotypes IGF-2 (GG)/ PON-1 (TT) with OR 1.64741 (95 % CI 0.7388 – 3.6735) and IGF-2 (AA)/ PON-1 (TT) with OR 2.6733 (95 % CI 0.7579 – 9.4291) were more frequent in the PCOS group, whereas the genotype IGF-2 (AA)/ PON-1 (CC) did not occur in the PCOS group at all. According to the molecular analyses significant differences in serum parameters were identified.
Conclusion: This investigation indicates, that only the combined analyses of putative candidate genes allowed a genotype-phenotype correlation in PCOS.
Schlüsselwörter
polyzystisches Ovarsyndrom - PCOS - PON-1 - IGF-2 - Adipositas - Fettstoffwechsel
Keywords
polycystic ovary syndrome - PCOS - PON-1 - IGF-2 - adipositas - lipid metabolism
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Dr. rer. nat. J. Kotzka
Institut für Klinische Biochemie und Pathobiochemie, Deutsches
Diabetes Zentrum, Leibnitz Zentrum für Diabetes
Forschung an der Heinrich-Heine-Universität Düsseldorf
Auf‘m Hennekamp 65
40225 Düsseldorf
Email: jkotzka@ddz.uni-duesseldorf.de