Abstract：
Polycystic ovarian syndrome (PCOS) is a complex endocrine and metabolic condition with several potential causes. Insulin resistance is a hallmark of PCOS that often coexists with hirsutism, hyperandrogenism, being overweight, and hormonal imbalances. The functioning of multiple replication and transcription factors is regulated by tumor suppressor genes (TSGs), which play a crucial role in maintaining genomic integrity and controlling the cell cycle of granulosa cells. In the present study, we examined how three single nucleotide polymorphisms (SNPs) in TP53, a cell cycle regulatory gene, affect the risk of developing PCOS in a sample of an Iranian population. Genomic DNA was extracted from 200 PCOS patients and 200 healthy women to analyze TP53 rs17880604, rs1625895, and rs1042522 SNPs using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Our findings revealed that the majority of PCOS cases were overweight [25 < body mass index (BMI) < 30]. A positive association was observed between the TP53 rs1042522 SNP and the risk of PCOS under codominant heterozygous and overdominant genetic patterns (odds ratio > 1). Meanwhile, a negative association was observed between TP53 SNPs (rs1625895, rs17880604) and susceptibility to PCOS under codominant heterozygous and dominant models of inheritance (odds ratio < 1). Moreover, different genotype and haplotype combinations of rs17880604/rs1625895/rs1042522 conferred a decreased risk of PCOS in our population. We found no statistical difference in the frequency of TP53 genotypes between PCOS cases and/or controls in terms of BMI, waist circumference, prolactin level, and markers of lipid and carbohydrate profile (P > 0.05). Molecular dynamic prediction showed that the missense substitution in the 17p13.1 position (rs1042522) could change the properties and secondary structure of the p53 protein. As inherited risk factors, TP53 variations may play a pivotal role in the pathogenesis of PCOS among Iranian women. Replicated population-based studies on other ethnicities are required to find the genetic contribution of variants of TP53, or SNPs located in other TSGs, to the etiology of this endocrine disease.
摘要：
多囊卵巢综合征（PCOS）是一种复杂的内分泌和代谢疾病，具有多种潜在原因。胰岛素抵抗是PCOS的一个标志，通常与多毛症共存，雄激素过多症,超重，荷尔蒙失衡。多种复制和转录因子的功能受肿瘤抑制基因（TSGs）的调节，在维持基因组完整性和控制颗粒细胞的细胞周期中起着至关重要的作用。在本研究中,我们研究了细胞周期调控基因TP53中的三个单核苷酸多态性（SNP）影响伊朗人群样本中患PCOS的风险。从200名PCOS患者和200名健康女性中提取基因组DNA，使用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法分析TP53rs17880604，rs1625895和rs1042522SNP。我们的研究结果表明，大多数PCOS病例超重[25<体重指数（BMI）<30]。TP53rs1042522SNP与显性杂合和显性遗传模式下PCOS风险之间呈正相关(比值比>1)。同时,在显性杂合和显性遗传模型下,TP53SNP(rs1625895,rs17880604)与PCOS易感性呈负相关(比值比<1).此外，rs17880604/rs1625895/rs1042522的不同基因型和单倍型组合降低了我们人群中PCOS的风险.我们发现，在BMI方面，PCOS病例和/或对照之间TP53基因型的频率没有统计学差异。腰围,催乳素水平,以及脂质和碳水化合物谱的标志物(P>0.05)。分子动力学预测表明，17p13.1位（rs1042522）的错义替换可以改变p53蛋白的性质和二级结构。作为遗传风险因素，TP53变异可能在伊朗女性PCOS的发病机制中起关键作用。需要对其他种族进行基于人群的重复研究，以发现TP53变体或位于其他TSG中的SNP的遗传贡献，这种内分泌疾病的病因。
