Research question

What is the association between VEGF gene sequence variants and its mRNA expression in recurrent pregnancy loss (RPL)? Vascular endothelial growth factor (VEGF) has a prominent role in pregnancy and affects pregnancy outcome. The association of VEGF gene 1154G>A, 634G>C and 583C>T polymorphic variations with cases of RPL and full-term fertile women as controls was investigated.

Design

Two hundred women with RPL and 240 women healthy controls were included. The restriction fragment length polymorphism method was used for genotyping and quantitative real-time polymerase chain reaction was used for analysis of mRNA expression.

Results

In VEGF 1154G>A, significant differences were found in homozygous AA genotype between case and control participants. The variant allele A frequency was significantly more abundant in RPL cases (0.41) than controls (0.19) (P < 0.0001). Only RPL cases with the multi-generation family history of miscarriages and those without any history showed significant differences of combined genotype GA+AA (P < 0.0001). In VEGF 634 G>C, CC genotype and allele C showed significantly increased frequency in RPL cases compared with healthy controls (P < 0.0001). The association between VEGF-1154 G>A SNP and VEGF-A mRNA expression levels was significant in RPL cases (P = 0.004). Also in VEGF-583 C>T, CT genotypes were seen significantly associated with cases (P = 0.003). The heterozygous genotype GA was significantly (P = 0.03) associated with upregulation and downregulation of VEGF mRNA, whereas the homozygous variant genotype AA only leads to low expression levels of VEGF mRNA in patients with RPL.

Conclusions

All the variants of VEGF play a vital role in an increased susceptibility to RPL. Also, VEGF-1154, AA genotypes are associated with its altered low mRNA expression in women with RPL and seem to affect pregnancy outcome.

中文翻译：

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VEGF基因序列变异及其在复发性流产中的表达

研究问题

VEGF基因序列变异与其在复发性妊娠丢失 (RPL) 中的 mRNA 表达之间有什么关联？血管内皮生长因子（VEGF）在妊娠中具有重要作用并影响妊娠结局。研究了VEGF基因 1154G>A、634G>C 和 583C>T 多态性变异与 RPL 病例和作为对照的足月可育女性的关联。

设计

包括 200 名 RPL 女性和 240 名健康对照女性。限制性片段长度多态性方法用于基因分型，定量实时聚合酶链反应用于分析mRNA表达。

结果

在VEGF 1154G>A 中，病例和对照参与者之间的纯合 AA 基因型存在显着差异。RPL 病例 (0.41) 的变异等位基因 A 频率明显高于对照组 (0.19) ( P < 0.0001)。只有具有多代流产家族史的RPL病例与无流产史的RPL病例的GA+AA联合基因型有显着差异（P <0.0001）。在VEGF 634 G>C 中，与健康对照组相比，CC 基因型和等位基因 C 在 RPL 病例中的频率显着增加（P < 0.0001）。在 RPL 病例中，VEGF -1154 G>A SNP 和VEGF-A mRNA 表达水平之间存在显着相关性（P  = 0.004）。同样在 VEGF-583 C>T 中，CT 基因型与病例显着相关（P = 0.003）。杂合基因型 GA 与VEGF mRNA 的上调和下调显着相关（P = 0.03） ，而纯合变异基因型 AA 仅导致RPL 患者VEGF mRNA 的低表达水平。

结论

VEGF 的所有变体在增加对 RPL 的易感性中都起着至关重要的作用。此外，VEGF -1154、AA 基因型与其在 RPL 女性中改变的低 mRNA 表达有关，并且似乎影响妊娠结果。