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BackgroundVascular endothelial growth factor (VEGF) contributes to the pathogenesis of polycystic ovary syndrome (PCOS), and genetic variations in VEGFA gene were suggested to contribute to VEGF secretion and PCOS.AimTo evaluate the association of altered VEGF levels, stemming from the presence of specific VEGFA variants, with altered risk of PCOS.Subjects and MethodsRetrospective case-control study, performed between 2012–2015. Study subjects comprised 382 women with PCOS, and 393 control subjects. ELISA measured VEGF levels; genotyping of VEGFA variants was done by allelic exclusion.ResultsAmong the 12 tested VEGFA SNPs, minor allele frequency of only rs3025020 was significantly higher in PCOS cases than control women. Increased and reduced PCOS risk was seen with rs3025020 and rs2010963 genotypes, respectively. Increases and reduction in VEGF levels were associated with rs3025020 and rs2010963, respectively. Increased fasting insulin and HOMA-IR, and bioactive testosterone were linked with rs3025020, while carriage of rs2010963 was linked with reduction in fasting insulin, and free and bioactive testosterone. Of the 12 VEGFA variants, 9 were in LD, thus allowing construction of 9-locus haplotypes. Increased frequency of CAACAGCGA haplotype was seen in PCOS cases, after controlling for BMI, free and bioactive testosterone, SHBG, free insulin and HOMA-IR.ConclusionThis study confirms the contribution of altered VEGF secretion, resulting from genetic variation in VEGFA gene into the pathogenesis of PCOS. This supports a role for VEGF as PCOS candidate locus.

ProblemWe investigated the association between idiopathic recurrent pregnancy loss (RPL) and HLA‐DPB1, HLA‐DQB1, and HLA‐DRB1 alleles and DPB1‐DQB1‐DRB1 haplotypes.Method of studyCase‐control retrospective study involved 93 Lebanese women with unexplained RPL, and 113 multiparous Lebanese women with two or more successful pregnancies, and no miscarriages who served as controls. DPB1, DQB1, and DRB1 genotyping was performed by PCR‐SSP.ResultsExpected and observed DRB1, DQB1, and DPB1 frequencies were comparable, and HLA genotype frequencies were in Hardy‐Weinberg equilibrium. Significantly higher frequencies of DRB1*04:01:01 and DRB1*08:01:01, and decreased DRB1*07:01:01 frequency were seen in RPL cases than in controls. On the other hand, the distribution of DQB1 alleles was comparable between cases and control groups. Significantly lower frequencies of DPB1*04:01:01 and DPB1*14:01:01 were seen in women with RPL than control subjects. While the frequency DPB1*02:01:01 was markedly higher in RPL cases than in controls, the difference was not significant. DPB1‐DQB1‐DRB1 haplotype analysis identified haplotype DPB1*04:01:01‐DQB1*03:02:01‐DRB1*04:01:01 to be positively associated, while haplotype DPB1*04:01:01‐DQB1*02:01:01‐DRB1*07:01:01 to be negatively associated with RPL. Of these two haplotypes, only DPB1*04:01:01‐DQB1*02:01:01‐DRB1*07:01:01 remained significant after correction for multiple tests (Pc = .0008).ConclusionOur results confirm an association of select DRB1 and DPB1 alleles with RPL in Lebanese women, and the first to identify DPB1‐DQB1‐DRB1 linked with altered RPL susceptibility, further highlighting the immunological/inflammatory nature of RPL.

Background: Decreased sex hormone-binding globulin (SHBG) levels were associated with polycystic ovary syndrome (PCOS). SHBG polymorphisms associated with reduced SHBG production were tested for their association with PCOS, but with inconclusive results. We tested whether altered SHBG levels and SHBG variants were associated with PCOS. Methods: The study subjects included 242 women with PCOS and 238 control women. SHBG genotyping was done by real-time PCR. Results: Higher minor allele frequency of rs13894, rs858521 and rs727428 was seen in PCOS cases, and significant differences in rs858521 and rs727428 genotypes distribution were seen between PCOS cases and controls. Multivariate regression analysis confirmed the association of only rs727428 with PCOS. Though it was not statistically significant, serum SHBG levels were reduced according to rs727428 genotypes in PCOS cases than in controls. Carriage of rs727428 minor allele was associated with significant increases in free/bioactive testosterone in PCOS cases. Seven-locus (rs9898876-rs13894-rs858521-rs1799941-rs6257-rs6259-rs727428) haploview analysis showed increased frequency of GCCGTGA, GTCGTGA and GTCATGG, and reduced frequency of GTCGTGG haplotypes in PCOS cases than in controls, thus conferring disease susceptibility and protective nature to these haplotypes, respectively. Conclusion: Specific SHBG variants affecting serum SHBG levels and SHBG haplotypes are associated with PCOS, suggesting the role for SHBG as PCOS candidate gene.

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