Gene-gene interactions and risk of recurrent miscarriages in carriers of endocrine gland–derived vascular endothelial growth factor and prokineticin receptor polymorphisms

• Published in: Fertility and sterility Vol. 102; no. 4; pp. 1071 - 1077.e3
• Main Authors: Su, Mei-Tsz, Lin, Sheng-Hsiang, Chen, Yi-Chi, Kuo, Pao-Lin
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2014
• Subjects: Abortion, Habitual - genetics; Adult; Case-Control Studies; EG-VEGF; Epistasis, Genetic; Female; Gastrointestinal Hormones - genetics; Gene Frequency; gene polymorphism; Gene-gene interaction; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Internal Medicine; Obstetrics and Gynecology; Phenotype; Polymorphism, Genetic; Pregnancy; prokineticin receptor; Receptors, G-Protein-Coupled - genetics; Receptors, Peptide - genetics; recurrent miscarriage; Risk Factors; Vascular Endothelial Growth Factor, Endocrine-Gland-Derived - genetics; EG-VEGF; recurrent miscarriage; gene polymorphism; prokineticin receptor; Gene-gene interaction
• ISSN: 0015-0282; 1556-5653; 1556-5653
• DOI: 10.1016/j.fertnstert.2014.06.042

To study endocrine gland–derived vascular endothelial growth factor (EG-VEGF), prokineticin receptor (PROKR) 1, and PROKR2 variants in the coding regions of idiopathic recurrent miscarriage (RM) patients and further evaluate gene-gene interactions of these three genes. Case-control study. University-based reproductive clinics and genetics laboratory. A total of 142 women with a history of idiopathic RM and 149 control subjects were included. None. All blood samples were nucleotide sequenced in the coding regions of EG-VEGF, PROKR1, and PROKR2. Gene-gene interaction of three gene variants was evaluated with the use of the multifactor dimensionality reduction method. One nonsynonymous variant of each of the three genes was identified, and PROKR1 (I379V) and PROKR2 (V331M) were significantly associated with idiopathic RM. Genetic interactions were found not only between PROKR1 (I379V) and PROKR2 (V331M), but also among EG-VEGF (V67I), PROKR1 (I379V), and PROKR2 (V331M). Women carrying low-risk genotypes had a 77% reduced risk of experiencing miscarriages compared with those carrying high-risk genotypes. The present study corroborates the clinical relevance of the EG-VEGF system in human early pregnancy, and provides evidence for the gene-gene interactions of EG-VEGF and PROKR variants.