-675 4G/5G纤溶酶原激活物抑制剂-1和-2518A/G单核细胞趋化蛋白-1基因多态性与克什米尔女性多囊卵巢综合征的关联：一项病例对照研究。
Association of -675 4G/5G PAI-1 and -2518A/G MCP-1 genetic polymorphisms with polycystic ovary syndrome in Kashmiri women: A case control study.
作者信息
Yousuf Syed Douhath, Ganie Mohammad Ashraf, Mudassar Syed, Shafi Humiara, Ibrahim Saima, Jeelani Humira, Rashid Gowhar, Zargar Mohammad A, Rashid Fouzia
机构信息
Department of Clinical Biochemistry, Sher-i-Kashmir Institute of Medical Sciences (SKIMS), Jammu and Kashmir, India.
Department of Endocinology, Sher-i-Kashmir Institute of Medical Sciences (SKIMS), Jammu and Kashmir, India.
出版信息
J Family Med Prim Care. 2022 Aug;11(8):4743-4752. doi: 10.4103/jfmpc.jfmpc_1916_21. Epub 2022 Aug 30.
BACKGROUND
Polycystic ovarian syndrome (PCOS) is a highly prevalent endocrine disorder among females of fertile age. It has been speculated to be associated with low-grade chronic inflammation like other inflammatory response-driven multifactorial illnesses such as diabetes mellitus (DM) and cancer. Monocyte chemoattractant protein-1 (MCP-1) and plasminogen activator inhibitor-1 (PAI-1) are biomarkers of inflammation and endothelial dysfunction, respectively. These have been found to be elevated in PCOS patients. The current research reveals that single nucleotide polymorphisms (SNPs) in their genes are strongly associated with the elevation of these biomarkers. The goal of this study was to see if there was a link between PAI-1 -675 4G/5G and MCP-1 -2518 A/G polymorphisms with the occurrence of PCOS.
MATERIAL AND METHOD
This study included 220 PCOS participants and 220 healthy controls. The allele-specific polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods were used to investigate PAI-1-675 4G/5G and MCP-1 -2518A/G SNPs, respectively.
RESULTS
The -675 4G/5G SNP in the PAI-1 gene was strongly linked to PCOS. The odds ratio (OR) for the 4G/4G genotype was (OR = 3.2; = 0.001), whereas the OR for the 4G/5G genotype was (OR = 2.39; = 0.001). The carriers with the 4G/4G and 4G/5G genotypes showed significantly increasing trends in the triglyceride levels ( < 0.05). The genotypic frequency of the -2518 A/G MCP-1 SNP differed significantly between the PCOS patients and healthy controls; the GG genotype remained a strong predictor of PCOS (OR = 8.7; = 0.01) and the AG genotype (OR = 2.40; = 0.01), indicating an elevated risk of predisposing women to PCOS. There was a significant variation in the glucose 2-h levels between -2518A/G MCP-1 genotypes with AG heterozygous and GG mutant genotype showing increasing trends of glucose 2-h levels ( < 0.05).
CONCLUSION
Both PAI-1 -675 4G/5G and MCP-1 -2518A/G polymorphisms are associated with predisposition to PCOS and its complications in Kashmiri women.
背景
多囊卵巢综合征（PCOS）是育龄女性中一种高度普遍的内分泌紊乱疾病。据推测，它与低度慢性炎症有关，如同其他由炎症反应驱动的多因素疾病，如糖尿病（DM）和癌症。单核细胞趋化蛋白-1（MCP-1）和纤溶酶原激活物抑制剂-1（PAI-1）分别是炎症和内皮功能障碍的生物标志物。已发现这些标志物在PCOS患者中升高。当前研究表明，它们基因中的单核苷酸多态性（SNP）与这些生物标志物的升高密切相关。本研究的目的是探讨PAI-1 -675 4G/5G和MCP-1 -2518 A/G多态性与PCOS发生之间是否存在关联。
材料与方法
本研究纳入了220名PCOS参与者和220名健康对照者。分别采用等位基因特异性聚合酶链反应（PCR）和限制性片段长度多态性（RFLP）方法检测PAI-1 -675 4G/5G和MCP-1 -2518A/G SNP。
结果
PAI-1基因中的 -675 4G/5G SNP与PCOS密切相关。4G/4G基因型的优势比（OR）为（OR = 3.2；P = 0.001），而4G/5G基因型的OR为（OR = 2.39；P = 0.001）。携带4G/4G和4G/5G基因型的个体甘油三酯水平呈显著上升趋势（P < 0.05）。PCOS患者和健康对照者之间 -2518 A/G MCP-1 SNP的基因型频率存在显著差异；GG基因型仍然是PCOS的强预测指标（OR = 8.7；P = 0.01），AG基因型（OR = 2.40；P = 0.01），表明女性患PCOS的风险升高。 -2518A/G MCP-1基因型之间的2小时血糖水平存在显著差异，AG杂合基因型和GG突变基因型的2小时血糖水平呈上升趋势（P < 0.05）。
结论
PAI-1 -675 4G/5G和MCP-1 -2518A/G多态性均与克什米尔女性患PCOS及其并发症的易感性相关。
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