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分析 VEGF 基因多态性与血清 VEGF 蛋白水平对多囊卵巢综合征患者的影响。

Analysis of VEGF gene polymorphisms and serum VEGF protein levels contribution in polycystic ovary syndrome of patients.

机构信息

The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China.

出版信息

Mol Biol Rep. 2019 Dec;46(6):5821-5829. doi: 10.1007/s11033-019-05015-y. Epub 2019 Aug 5.

Abstract

Vascular endothelial growth factor (VEGF) is a well-known factor in reproductive function and contributes to the pathogenesis of polycystic ovary syndrome (PCOS). Genetic variations in VEGFA gene were suggested to contribute alterations in VEGF secretion and PCOS. This study evaluated the association of VEGFA SNPs with altered VEGF secretion level and PCOS among ethnically-matched control women. This prospective case-control study was conducted from 2016 to 2018 and comprised of 55 women with PCOS and 52 control subjects. ELISA was used to measure VEGF levels; and various other related bio chemicals whereas the genotyping of VEGFA variants was performed through the analysis of nine SNPs of VEGF. PRL, E2, PRGE testosterone and glucose level were found to be insignificantly different. The levels of FSH, LH, LH/FSH, TT, insulin, SHBG and HOMA-IR were significantly higher in the study group. Among the nine tested variants of VEGF SNPs, two SNPs rs3025020 and rs833061, consisted of TT (Recessive and Dominant homozygous, respectively) which were marginally higher in test. The SNP rs1570360 had significantly higher GG allele (32.73%) which was recessive homozygous. There was no significant difference observed in genotype frequencies related to higher value of VEGF. The genotype frequencies for the studied SNPs were in alignment with Hardy-Weinberg equilibrium (HWE). The mean serum VEGF levels got significantly increased in PCOS group. No significant association was found between VEGF genotypes and its serum levels. VEGF levels in rs699947 (AA-major homozygous), rs3025039 (CC-major homozygous) and rs833061 (TT & CC-major & minor homozygous) genotypes were significantly higher in PCOS. The study results evidently proved that the allelic variants in genes may be a factor for PCOS and VEGF serum levels with respect to few SNP variants only. These findings indicated that VEGF may be involved in PCOS status and confirmed the previous association between genetic variants in VEGF, serum level of VEGF protein and PCOS.

摘要

血管内皮生长因子(VEGF)是生殖功能中众所周知的一个因素,有助于多囊卵巢综合征(PCOS)的发病机制。VEGFA 基因的遗传变异被认为会导致 VEGF 分泌的改变和 PCOS。本研究评估了 VEGFA SNP 与同种族匹配的对照女性中改变的 VEGF 分泌水平和 PCOS 的关联。这项前瞻性病例对照研究于 2016 年至 2018 年进行,包括 55 名 PCOS 女性和 52 名对照受试者。使用 ELISA 测量 VEGF 水平;并分析了其他各种相关生物化学物质,而 VEGFA 变体的基因分型则通过分析 VEGF 的九个 SNP 来进行。PRL、E2、PRGE 睾酮和葡萄糖水平无显著差异。研究组的 FSH、LH、LH/FSH、TT、胰岛素、SHBG 和 HOMA-IR 水平显著升高。在测试的 9 个 VEGF SNP 变体中,两个 SNP rs3025020 和 rs833061 分别为 TT(分别为纯合子和显性纯合子),其值略高。SNP rs1570360 具有显著较高的 GG 等位基因(32.73%),为隐性纯合子。与 VEGF 更高值相关的基因型频率无显著差异。研究 SNP 的基因型频率与 Hardy-Weinberg 平衡(HWE)一致。PCOS 组的血清 VEGF 水平显著升高。VEGF 基因型与血清水平之间未发现显著关联。rs699947(AA-主要纯合子)、rs3025039(CC-主要纯合子)和 rs833061(TT 和 CC-主要和次要纯合子)基因型的 VEGF 水平显著升高。研究结果清楚地证明了基因中的等位基因变体可能是 PCOS 和 VEGF 血清水平的一个因素,仅涉及少数 SNP 变体。这些发现表明 VEGF 可能参与 PCOS 状态,并证实了之前关于 VEGF 遗传变异、VEGF 蛋白血清水平和 PCOS 之间的关联。

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