Transforming growth factor beta 1 (TGFβ1) polymorphisms and unexplained infertility: A genetic association study
Transforming growth factor beta 1 (TGFβ1) polymorphisms and unexplained infertility: A genetic association study
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DOI：
10.1080/19396368.2020.1773575
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发表时间：
2020-07-30
影响因子：
2.4
通讯作者：
Amani, Davar
中科院分区：
文献类型：
--
作者：
Marhemati, Farnaz;Rezaei, Ramazan;Amani, Davar
不孕症的发病率正在上升，令人担忧。约10%至30%的不孕症被归类为特发性或不明原因不孕症（UI）。tgf - β是一种多功能的免疫调节细胞因子，在妊娠期间调节滋养细胞对细胞外基质的着床和粘附。本研究的目的是研究伊朗不明原因不孕症患者中tgf - β 1基因rs1800470 （C29T）和rs1800471 （G74C）两种多态性之间的关系。共有250名尿失禁患者和484名无不育史的健康个体纳入研究。目的DNA片段的扩增和测序分别采用PCR和自动测序方法。利用新的计算机工具分析了这些多态性对tgf - β 1 mRNA和蛋白质结构和功能的影响。rs1800470和rs1800471多态性的等位基因、基因型和单倍型的频率分布在受试者和对照组之间有统计学差异。tgf - β 1 rs1800470 (29C -> T) CC基因型增加男性尿失血性患者发生尿失血性的风险。此外，tgf - β 1 rs1800471的C等位基因与女性UI患者的UI风险增加有关。夫妇、亚组分析显示，tgf - β 1多态性（rs1800470、rs1800471）与男性、女性和所有UI患者的UI风险之间存在显著关联。UI组与健康组TG、CG单倍型频率差异有统计学意义（P < 0.05）。RS1800471多态性改变了tgf - β 1 mRNA的二级结构，导致一个mRNA臂的去除和两个新臂的产生。综上所述，目前的研究结果表明，attgf - β 1功能多态性可能在伊朗人群对UI的易感性中起重要作用。根据计算机分析，tgf - β 1的多态性可以缩短mRNA的半衰期，从而降低tgf - β 1的表达。
The prevalence of infertility is increasing and worrisome. About 10 to 30% of infertility is classified as idiopathic or unexplained infertility (UI). TGF-beta is multifunctional and immunoregulatry cytokine which regulates both implantation and adhesion of trophoblasts to the extracellular matrix during pregnancy. The aim of the current study was to investigate the association between two polymorphisms rs1800470 (C29T) and rs1800471 (G74C) of the TGF-beta 1 gene in Iranian patients with unexplained infertility. A total of 250 UI patients and 484 healthy individuals with no history of infertility were included in the study. The amplification and sequencing of target DNA fragments were done using PCR and automated sequencing methods, respectively. The effects of these polymorphisms on both TGF-beta 1 structure and function of mRNA and protein were analyzed using new in-silico tools. The frequency distribution of the alleles, genotypes, and haplotypes of both rs1800470 and rs1800471 polymorphisms had a statistically significant difference between subjects and controls. CC genotype of TGF-beta 1 rs1800470 (29C -> T) increase the risk of UI in male UI patients. Moreover, C alleles of TGF-beta 1 rs1800471 was associated with increased risk of UI in female UI patients. Couples, subgroup analysis revealed a significant association between TGF-beta 1 polymorphisms (rs1800470, rs1800471) and the risk of UI in male, female, and all UI patients. The frequency of TG and CG haplotypes were statistically different in both UI and healthy subjects group (P < 0.05). RS1800471 polymorphisms changed the secondary structure ofTGF-beta 1 mRNA and resulted in the removal of one mRNA arm and creation of two new arms. Taken together, the results of the current study suggest thatTGF-beta 1 functional polymorphisms may play an important role in the susceptibility to UI in Iranian population. According to in silico analysis, polymorphisms in TGF-beta 1 can reduce mRNA half-life and, therefore, reduced TGF-beta 1 expression.