lunes, 25 de enero de 2016

Vascular endothelial growth factor pathway in endometriosis: genetic variants and plasma biomarkers. - PubMed - NCBI

2016 Jan 7. pii: S0015-0282(15)02185-8. doi: 10.1016/j.fertnstert.2015.12.016. [Epub ahead of print]

Vascular endothelial growth factor pathway in endometriosis: genetic variants and plasma biomarkers.

Vodolazkaia A1, Yesilyurt BT2, Kyama CM3, Bokor A4, Schols D5, Huskens D5, Meuleman C6, Peeraer K6, Tomassetti C6, Bossuyt X1, Lambrechts D2,D'Hooghe T7, Fassbender A8.

Author information

Abstract

OBJECTIVE:

To study single nucleotide polymorphisms (SNPs) involved in angiogenesis (VEGF, PLGF, VEGFR1, VEGFR2, HIF-1α) and plasma levels of the corresponding proteins (VEGF, PLGF, sVEGFR1, sVEGFR2) in women with and without endometriosis.

DESIGN:

Allele frequencies of vascular endothelial growth factor (VEGF) pathway SNPs and plasma levels of the corresponding proteins were investigated in patients with endometriosis and in controls.

SETTING:

University hospital.

PATIENT(S):

Samples of DNA from 1,931 Caucasian patients were included (1,109 patients with endometriosis and 822 controls). An additional study group included 973 DNA samples from volunteers, self-reported to be healthy without laparoscopic evaluation.

INTERVENTION(S):

Women who underwent a laparoscopy for subfertility and/or pain and healthy volunteers without laparoscopic evaluation.

MAIN OUTCOME MEASURE(S):

Functional SNPs of the VEGF, VEGFR1, VEGFR2, HIF-1α genes and Hap Map tagging SNPs of the PLGF gene were genotyped by using iPLEX technology on a Sequenom MassArray and TaqMan SNP Genotyping Assay. The VEGF levels were determined in ethylenediaminetetraacetic acid plasma samples by using Bio-Plex Protein Array System. PLGF, sVEGFR1, and sVEGFR2 levels were measured in ethylenediaminetetraacetic acid plasma samples by using ELISA Quantikine kits.

RESULT(S):

A significant association was found between the rs2268613 polymorphism in the PLGF gene and PLGF plasma levels. In all study subjects, women with the AA variant of the rs2268613 PLGF gene had significantly lower PLGF plasma levels (median [interquartile range] 9.36 [8.19-10.43] pg/mL) than those with the AG variant (12.1 [11.81-20.84] pg/mL; Pa=.0085, Pb=.04), both before and after multiple testing. Plasma levels of VEGF were elevated in endometriosis patients (especially in minimal-mild endometriosis during the menstrual cycle phase) compared with laparoscopic controls but had a moderate diagnostic performance (area under the curve, 0.73) in this discovery dataset. At a cut-off plasma level of VEGF >3.88 pg/mL, minimal-mild stages of endometriosis were diagnosed with a sensitivity of 74% and a specificity of 80% during the menstrual phase of cycle. The associations between the presence of endometriosis and SNPs in PLGF (rs2268614), HIF-1α (rs11549465), and VEGFR1 (rs9582036) genes lost statistical significance after multiple testing.

CONCLUSION(S):

Genetic variants in the PLGF rs2268613 gene may influence plasma levels of the corresponding protein. Plasma levels of VEGF were elevated in endometriosis patients compared with controls. The associations between the presence of endometriosis and SNPs in PLGF (rs2268614), HIF-1α (rs11549465), and VEGFR1 (rs9582036) genes lost statistical significance after multiple testing.