| Summary: | Abstract Background 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. Methods 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. Results 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. Conclusions 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.
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