title: Association of VEGFA gene polymorphisms and VEGFA plasma levels with spontaneous preterm birth.
abstract: BACKGROUND
  Angiogenic pathway regulating genes such as vascular endothelial growth factor A (VEGFA) have been implicated in preterm birth (PTB) complications. Research shows that the VEGFA/VEGF receptor system plays an important role in the regulation of circulating progesterone level. Attenuation of VEGFA signaling at mid pregnancy results in onset of labor and parturition because of a reduction in circulating progesterone levels. The aim of this study was to investigate the association of VEGFA gene polymorphisms (rs2010963, rs3025039, rs699947, and rs10434) with spontaneous PTB and VEGFA plasma levels in preterm and term women.
  
  
  METHODS
  Peripheral maternal blood from 495 women was used for extraction of DNA and genotyping was carried out using the SequenomMassARRAY platform. Maternal plasma was used to measure VEGFA levels.
  
  
  RESULTS
  Results showed a significant association between rs2010963 variants and PTB at both allelic and genotypic levels. The frequencies of CG and GG genotypes were significantly higher in the preterm group (96%) than in the term group (87%) (P=0.012). The odds of the G allele occurring among the preterm group was 1.8 times higher than those in the term group (odds ratio 1.8, 95% confidence interval 1.2-2.6, P=0.003). After adjustment for Bonferroni correction, the association between rs2010963 variants and PTB remained significant (P=0.004). The rs69947 was associated with PTB at a nominal significance level (P=0.030). There was no significant association between rs3025039, rs10434, and PTB in this population. VEGFA gene polymorphisms were not associated with VEGFA plasma levels. This study indicated for the first time that the VEGFA rs2010963 polymorphisms may play a potential role in preterm complications.
authors.affiliation: aPharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine bDepartment of Obstetrics and Gynecology, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Immaculate Mbongo
authors.initials: IM
authors.lastname: Langmia
authors.forename: Yamunah D
authors.initials: YD
authors.lastname: Apalasamy
authors.forename: Siti Z
authors.initials: SZ
authors.lastname: Omar
authors.forename: Zahurin
authors.initials: Z
authors.lastname: Mohamed
mesh_terms: D000328:Adult; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D047928:Premature Birth / Q000097:blood* / Q000235:genetics*; D012189:Retrospective Studies; D042461:Vascular Endothelial Growth Factor A / Q000097:blood* / Q000235:genetics*
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A