Association of genetic polymorphism of vascular endothelial growth factor in the etiology of recurrent pregnancy loss: a triad study
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The study estimates the association of VEGF gene polymorphism (-1154 G/A, -2549 I/D, -2578 C/A, and +936 C/T) in recurrent pregnancy loss from South Indian population.
A total of 100 couples with the history of recurrent pregnancy loss and 100 couples with medically terminated pregnancies were considered. Fetal tissues with < 20 weeks of gestation including peripheral blood from case and control couples were collected. VEGF gene polymorphisms were determined by allele-specific polymerase chain reaction. Genotypic distribution and allele frequencies were evaluated by odds ratio with 95% confidence intervals. Haplotype analysis was done to determine the association of specific haplotypes with recurrent pregnancy loss.
The VEGF -1154 G/A polymorphism was significantly prevalent in the aborted fetuses and in their mothers whereas -2549 I/D polymorphism was significantly higher in the aborted fetuses while the + 936 C/T polymorphism showed prevalence in the case mothers revealing their statistically significant association to recurrent pregnancy loss. A1154D2549A2578T936 haplotype showed an increased risk in case fetuses and mothers whereas A1154D2549C2578C936, in case mothers and fathers while haplotype G1154I2549A2578C936 found a protective association in the case fetuses compared to controls.
This is the first report of family-based triad study revealing a significant association of VEGF gene polymorphism in the etiology of recurrent pregnancy loss.
KeywordsRecurrent pregnancy loss AS-PCR VEGF Polymorphism Fetus
The present work was greatly supported by the Senior Research Fellowship granted by the Indian Council of Medical Research, New Delhi (ICMR–45/1/2014-HUM-BMS).
Compliance with ethical standards
The study was approved by the Ethical Committee of Institute of Genetics, Osmania University (Approval No: 69/IG/IEC/2014 dt 13/08/2014). Demographic details with an informed written consent were obtained before the sample collection from all the subjects.
Conflict of interest
The authors declare that they have no conflict of interest.
- 5.Ferrara N, Gerber HP, Couter JL. The biology of VEGF and its receptors. Nature. 2003;9:669–76.Google Scholar
- 7.Medford AR, Godinho SI, Keen LJ, Bidwell JL, Millar AB. Relationship between vascular endothelial growth factor + 936 genotype and plasma/epithelial lining fluid vascular endothelial growth factor protein levels in patients with and at risk for ARDS. Chest. 2009;136:457–64. https://doi.org/10.1378/chest.09-0383.CrossRefGoogle Scholar
- 10.Jelkmann W. Pitfalls in the measurement of circulating vascular endothelial growth factor. Clin Chem. 2001;47:617–23.Google Scholar
- 14.Tischer E, Mitchell R, Hartman T, et al. The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing. J Biol Chem. 1991;266:11947–54.Google Scholar
- 19.Xu X, Du C, Li H, Du J, Yan X, Peng L, et al. Association of VEGF genetic polymorphisms with recurrent spontaneous abortion risk: a systematic review and meta-analysis. 2015. https://doi.org/10.1371/journal.pone.0123696.
- 21.Eller AG, Branch DW, Nelson L, Porter TF, Silver RM. Vascular endothelial growth factor-A gene polymorphisms in women with recurrent pregnancy loss. J Reprod Immunol. 2011;88:48–52. https://doi.org/10.1016/j.jri.2010.06.159.
- 24.Pereza N, Ostojic S, Smircic A, Hoziic A, Kapovic M, Peterlin B. The −2549 insertion/deletion polymorphism in the promoter region of the VEGFA gene in couples with idiopathic recurrent spontaneous abortion. J Assist Reprod Genet. 2015;32:1789–94. https://doi.org/10.1007/s10815-015-0593-0.CrossRefGoogle Scholar
- 26.Yalcintepe SA, Silan F, Hacivelioglu SO, Uludag A, Cosar E, Ozdemir O. Fetal Vegf genotype is more important for abortion risk than mother genotype. Int J Mol Cell Med. 2014;3(2):88–9.Google Scholar