Almasoudi Kholoud S, Hussain Eram, Almotairi Reema, Bhat Tanzeela, Mtiraoui Nabil, Ezzidi Intissar, Mir Rashid
Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Prince Fahad Bin Sultan Chair for Biomedical Research, University of Tabuk, Tabuk 71491, Saudi Arabia.
Laboratory of Human Genome and Multifactorial Diseases, Faculty of Pharmacy, University of Monastir, Monastir 5000, Tunisia.
Life (Basel). 2024 Jul 28;14(8):949. doi: 10.3390/life14080949.
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.
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.
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 ( < 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 < 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 < 0.05. Likewise, the CXCR2 (CA+AA) vs CC genotype was associated with increased susceptibility to PCOS, with OR 2.25, < 0.032.
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.
多囊卵巢综合征（PCOS）是一种具有复杂病理生理学的异质性、多因素内分泌紊乱疾病。它是一种全球范围内发病率不断上升的不孕症疾病，影响着很大比例的育龄妇女，患病率相对较高，为8% - 13%。全基因组关联研究已经揭示了基因变异与包括PCOS在内的许多疾病之间的关联。白细胞介素8（IL8）的细胞活性由受体CXC趋化因子受体2（CXCR2）介导，IL8的转录由肿瘤坏死因子-α（TNF-α）控制。因此，本研究旨在探讨TNF-α、CCR5 - Δ32和CXCR2基因变异与PCOS的关联。
在这项病例对照研究中，我们使用扩增阻滞突变系统（ARMS）-聚合酶链反应（PCR）来检测和确定研究对象中多态性变体TNF-α、CCR5 - Δ32和CXCR2的存在。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。
病例对照研究的结果显示，在调查中检测的大多数生化和内分泌血清生物标志物——包括脂质（低密度脂蛋白、高密度脂蛋白和胆固醇）、2型糖尿病标志物（空腹血糖、游离胰岛素和稳态模型评估胰岛素抵抗指数）以及激素（促卵泡生成素、促黄体生成素、睾酮和孕酮）——在PCOS患者中呈现出具有统计学意义的变化。在所考虑人群的PCOS患者和健康对照中分析的TNF-α（rs1800629）、CCR5 - Δ32和CXCR2（rs2230054）基因型分布具有显著性（<0.05）。CXCR2 - CA、TNF-α GA和CCR5（野生型+Δ32*）基因型的杂合性与PCOS易感性显著相关，在共显性模型中具有高比值比（OR）且<0.05。同样，TNF-α和CXCR2基因的A等位基因以及CCR5Δ32*（突变）等位基因与PCOS易感性显著相关，具有高OR且<0.05。同样，CXCR2（CA + AA）与CC基因型相比与PCOS易感性增加相关，OR为2.25，<0.032。
我们的研究得出结论，TNF-α rs1800629G>A、CXCR2 - rs2230054C>T和CCR5 - Δ32 rs333是塔布克人群中发生PCOS的潜在位点。这些发现最终可能有助于识别和分类那些有PCOS风险的人群。为了验证这些结果，建议在不同种族人群中进行更大样本量的进一步纵向研究。
