title: Vascular endothelial growth factor (VEGFA) gene variation in polycystic ovary syndrome in a Tunisian women population.
abstract: Polycystic ovary syndrome (PCOS) is characterized by the growth of a number of small cysts on the ovaries which leads to sex hormonal imbalance. Women who are affected by this syndrome suffer from irregular menstrual cycles, decline in their fertility, excessive hair growth, obesity, acne and most importantly cardiac function problems. The vascular endothelial growth factor (VEGF) plays a pivotal role in tissue vascularization in general and in the pathogenesis of many diseases. The PCOS was found to be associated with high expression levels of VEGF. In women who undergo assisted reproductive procedures (ART), VEGF was found to be a key mediator of other factors to control ovary angiogenesis. Here, we set out to examine the association of VEGFA gene polymorphism with PCOS and its components in a population of Tunisia women to enhance our understanding of the genetic background leading angiogenesis and vascularization abnormalities in PCOS.
  
  
  
  The association of VEGFA gene with PCOS and its components was examined in a cohort of 268 women from Tunisia involving 118 PCOS patients and 150 controls. VEGFA gene variations were assessed through the analysis of the following SNPs rs699947 (A/C), rs833061 (C/T), rs1570360 (G/A), rs833068 (G/A), rs3025020 (C/T), and rs3025039 (C/T). The linkage disequilibrium between SNPs was assessed using HAPLOVIEW software while combination of SNPs into haplotypes in the population and the reconstruction of the cladogram were carried-out by PHASE and ARLEQUIN programs, respectively. Genetic association and genotype-phenotype correlations were calculated by logistic regression and non-parametric tests (Kruskall-Wallis and Mann-Whitney tests), respectively, using StatView program.
  
  
  
  We observed 10 haplotypes in our studied cohort whereH1 (ACGG), H2 (ACAG), H7 (CTGG) and H8 (CTGA) were the most frequent. We observed the association of the genotype CT of the SNP rs30225039 with PCOS phenotype (P = 0.03; OR 95 % CI = 2.05 [1.07-3.90]) and a trend for correlation of the pair of haplotypes H2/H2 with prolactin levels in plasma (P = 0.077; 193.5 ± 94.3 vs 45.7 ± 7.2). These data are consistent with literature and highlight one more time the role of vascularization in the pathogeny of PCOS.
  
  
  
  LD pattern in VEGF locus showed a similar LD pattern between the Tunisian population and the CEU. More haplotypes in the Tunisian population than in CEU was observed (22 haplotypes vs 16 haplotypes) suggesting higher recombination rate in Tunisians. The study showed that there was any advantage of using haplotypes compared with SNPs taken alone.
authors: Laboratory of Human Genome and multifactorial diseases, LR12ES07, Faculty of Pharmacy of Monastir, University of Monastir, Monastir, Tunisia. assila.bensalem@gmail.com.
authors: Assila
authors: A
authors: Ben Salem
authors: Laboratory of Human Genome and multifactorial diseases, LR12ES07, Faculty of Pharmacy of Monastir, University of Monastir, Monastir, Tunisia.
authors: Fatma
authors: F
authors: Megdich
authors: University Hospital F. Hached, Unit of Reproductive Medicine, Sousse, Tunisia.
authors: Olfa
authors: O
authors: Kacem
authors: Laboratory of Human Genome and multifactorial diseases, LR12ES07, Faculty of Pharmacy of Monastir, University of Monastir, Monastir, Tunisia.
authors: Malek
authors: M
authors: Souayeh
authors: Department of Gyneco Obstetric, University Hospital F. Hached, Sousse, Tunisia.
authors: Faten
authors: F
authors: Hachani Ben Ali
authors: Laboratory of Human Genome and multifactorial diseases, LR12ES07, Faculty of Pharmacy of Monastir, University of Monastir, Monastir, Tunisia.
authors: Sondes
authors: S
authors: Hizem
authors: Laboratory of Human Genome and multifactorial diseases, LR12ES07, Faculty of Pharmacy of Monastir, University of Monastir, Monastir, Tunisia.
authors: Faouzi
authors: F
authors: Janhai
authors: University Hospital F. Hached, Unit of Reproductive Medicine, Sousse, Tunisia.
authors: Mounir
authors: M
authors: Ajina
authors: Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah, Saudi Arabia.
authors: Muhammad
authors: M
authors: Abu-Elmagd
authors: Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah, Saudi Arabia.
authors: Mourad
authors: M
authors: Assidi
authors: Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah, Saudi Arabia.
authors: Mohammed H
authors: MH
authors: Al Qahtani
authors: Laboratory of Human Genome and multifactorial diseases, LR12ES07, Faculty of Pharmacy of Monastir, University of Monastir, Monastir, Tunisia.
authors: Touhami
authors: T
authors: Mahjoub
mesh_terms: D000328:Adult; D000483:Alleles; D015415:Biomarkers; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D010641:Phenotype; D011085:Polycystic Ovary Syndrome / Q000175:diagnosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D012307:Risk Factors; D014416:Tunisia; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D015415:Biomarkers; D042461:Vascular Endothelial Growth Factor A
keywords: Genetic association; Haplotype; PCOS; Polymorphism; Prolactin; SNP; VEGFA