Genetic Variants of Vascular Endothelial Growth Factor and Risk for the Development of Endometriosis
Tarih
2010Yazar
Toptas, Bahar
Agachan, Bedia
Eraltan, Ilhan Yaylim
Isbir, Turgay
Attar, Erkut
Attar, Rukset
Kuran, Sibel Bulgurcuoglu
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Backround/Aims: Endometriosis is regarded as a complex disese, in which genetic and environmental factors contribute to the disease phenotype. Whether vascular endothelial growth factor (VEGF) -460 C/T and +405 G/C polymorphisms are associated with susceptibility to endometriosis was investigated. Patients and Methods: Diagnosis of endometriosis was made on the basis of laparoscopic findings. Stage of endometriosis was determined according to the Revised American Fertility Society classification. Sixty out of the 112 women enrolled had no endometriosis, 11 had mild or early-stage endometriosis and 41 had severe endometriosis. Polymerase chain reaction (PCR), restriction fragment length polymorphism and agarose gel electrophoresis techniques were used to determine the -460 C/T and +405 GIG genotypes. Results: The VEGF +405 GIG genotype frequencies among the cases and controls were CC 55.8% and 35%; GC 30.8% and 50.0%; GG 13.5% and 15.0%, respectively. The allelic frequencies were C 71.15% (cases) and 60.0% (controls) and G 28.8% (cases) and 40% (controls). Patients with endometriosis had a higher incidence of the VEGF +405 CC genotype compared with the controls (p=0.027). Women with VEGF +405 CC genotype had 2.3-fold higher risk for endometriosis. VEGF +405 GC genotype and G allele in the control group was higher than the endometriosis group (p=0.039, p=0.027 respectively). The VEGF 460 C/T genotype frequencies among the cases were CC 21.2%, CT 26.9% and IT 51.9%; the C and T allelic frequencies were 34.6% and 65.3%, respectively. The VEGF -460 genotype frequencies among the controls were CC 31.70%, CT 18.3% and TT 50.0%; the C and T allelic frequencies were 40.8% and 59.1%, respectively (p>0.05). There was linkage disequilibrium between VEGF -460 C/T and +405 GIG polymorphisms (D': 0.197, r(2)=0.013). We observed that the VEGF 460T/405C haplotype frequency was significantly higher in patients compared to controls (p=0.011). Conclusion: Our data suggest that the CC genotype of VEGF +405 and 460T/405C haplotypes of VEGF may be associated with the risk of endometriosis, but the G allele of VEGF +405 appears to be protective against endometriosis.
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