PCOS是一种异质性,具有复杂病理生理学的多因素内分泌紊乱。这是一种全球范围内不断上升的不孕症,影响了很大一部分育龄妇女,患病率相对较高,为8-13%。全基因组关联研究揭示了遗传变异与许多疾病的关联,包括PCOS。IL8的细胞活性由受体CXCR2介导,IL8的转录受TNF-α控制。因此,本研究旨在探讨TNF-α,PCOS的CCR5-delta32和CXCR2基因变异。
方法:在本病例对照研究中,我们使用扩增-难治性突变系统(ARMS)-PCR来检测和确定多态变体TNF-α的存在,研究对象中的CCR5-delta32和CXCR2。这些基因多态性可能是PCOS发病机制和治疗中的关键候选基因变体。
结果:病例对照研究的发现表明,研究中检查的大多数生化和内分泌血清生物标志物-包括脂质(LDL,HDL,和胆固醇),T2DM标志物(空腹血糖,游离胰岛素,和HOMA-IR),和激素(FSH,LH,睾丸激素,和孕酮)-在PCOS患者中表现出统计学上的显着变化。TNF-α的分布(rs1800629),CCR5-delta32和CXCR2(rs2230054)基因型分析在PCOS患者和健康对照人群中是显著的(p<0.05)。CXCR2-CA的杂合性,TNF-αGA,CCR5(WT+Δ32*)基因型与PCOS易感性显著相关,在共显性模型中具有高OR和p<0.05。同样,TNF-α和CXCR2基因的A等位基因,连同CCR5Δ32*(突变)等位基因,与PCOS易感性显著相关,具有高OR和p<0.05。同样,CXCR2(CA+AA)和CC基因型与PCOS易感性增加相关,OR为2.25,p<0.032。
结论:我们的研究得出结论,TNF-αrs1800629G>A,CXCR2-rs2230054C>T,CCR5-Delta32rs333是Tabuk人群中发展PCOS的潜在基因座。这些发现最终可能有助于识别和分类那些有PCOS风险的人。为了验证这些结果,建议在不同种族人群中进行进一步的纵向研究,并且样本量更大。
PCOS is a heterogeneous, multifactorial endocrine disorder with a complex pathophysiology. It is a globally rising infertility disorder that affects a large percentage of women of reproductive age, with a relatively high prevalence of 8-13%. Genome-wide association studies have revealed associations of genetic variations with many diseases, including PCOS. The cellular activity of IL8 is mediated by the receptor CXCR2, and transcription of IL8 is controlled by TNF-α. Therefore, this study aimed to investigate the association of TNF-α, CCR5-delta32, and CXCR2 gene variations with PCOS.
METHODS: In this case control study, we used amplification-refractory mutation system (ARMS)-PCR to detect and determine the presence of the polymorphic variants TNF-α, CCR5-delta32, and CXCR2 in the study subjects. These gene polymorphs may serve as critical candidate gene variants in PCOS pathogenesis and therapeutics.
RESULTS: The case-control study\'s findings revealed that the majority of the biochemical and endocrine serum biomarkers examined in the investigation-including lipids (LDL, HDL, and cholesterol), T2DM markers (fasting glucose, free insulin, and HOMA-IR), and hormones (FSH, LH, testosterone, and progesterone)-exhibited statistically significant changes in PCOS patients. The distributions of TNF-α (rs1800629), CCR5-delta32, and CXCR2 (rs2230054) genotypes analyzed within PCOS patients and healthy controls in the considered population were significant (p < 0.05). The heterozygosity of CXCR2-CA, TNF-α GA, and CCR5(WT+Δ32*) genotypes was significantly associated with PCOS susceptibility, with high OR and p < 0.05 in the codominant model. Similarly, the A allele of the TNF-α and CXCR2 genes, along with the CCR5Δ32*(mutant) allele, was significantly associated with PCOS susceptibility, with high OR and p < 0.05. Likewise, the CXCR2 (CA+AA) vs CC genotype was associated with increased susceptibility to PCOS, with OR 2.25, p < 0.032.
CONCLUSIONS: Our study concludes that TNF-α rs1800629G>A, CXCR2-rs2230054C>T, and CCR5-Delta32 rs333 are potential loci for developing PCOS in the Tabuk population. These findings might eventually be useful in identifying and classifying those who are at risk for PCOS. To validate these results, it is advised that further longitudinal studies be conducted in diverse ethnic populations and with larger sample sizes.