[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.


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.


CONCLUSIONS
This investigation indicates, that only the combined analyses of putative candidate genes allowed a genotype-phenotype correlation in PCOS.
Knebel
B
B
Institut für Klinische Biochemie und Pathobiochemie, Deutsches Diabetes Zentrum, Leibnitz Zentrum für Diabetes Forschung an der Heinrich-Heine-Universität Düsseldorf.
Janssen
O E
OE
Hahn
S
S
Nitzgen
U
U
Jacob
S
S
Haas
J
J
Mack
S
S
Müller-Wieland
D
D
Kotzka
J
J
D000328:Adult; D043303:Aryldialkylphosphatase / Q000235:genetics*; D015992:Body Mass Index; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D050356:Lipid Metabolism / Q000235:genetics; D016015:Logistic Models; D011085:Polycystic Ovary Syndrome / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics
D007335:Insulin-Like Growth Factor II; D043303:Aryldialkylphosphatase