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JOURNAL ARTICLE
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[Combined analyses of paraoxonase-1 and IGF-2 polymorphism in polycystic ovary syndrome].

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.

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