Abstract
Monocyte chemoattractant protein-1 (MCP-1) is a pivotal chemokine in the inflammatory response, which plays an important role in recruiting monocytes to sites of injury and infection. However, the exact mechanism of Mcp-1 associated with PCOS risk was unknown. In this study, we explored whether the Mcp-1 -2518G>A polymorphism increases the risk of PCOS. We performed a comparative study of -2518G>A polymorphism of the Mcp-1 gene with PCOS. In addition, luciferase reporter assay was performed to evaluate the Mcp-1 transcriptional activity. A strong association was observed between the -2518G>A polymorphism of Mcp-1 gene and PCOS (p-value = 0.016, odd ratio (OR) = 0.693). A p-value under 0.05 is considered statistically significant. The genotype and allelic frequencies were assumed to be in Hardy-Weinberg equilibrium (HWE). The luciferase assays in 2 cell lines showed that the Mcp-1 -2518G>A substitution can increase the expression of Mcp-1. MCP-1 levels in serum for PCOS group were significantly higher than those in serum for controls (p-value = 0.02). Furthermore, the patients carrying a genotype A/A had significantly increased levels of MCP-1 in serum compared with levels of the MCP-1 of the patients with genotypes G/G and G/A (p-value = 0.031). This is the first study on the genetic variation of the Mcp-1 gene and PCOS. This finding suggests that the Mcp-1 -2518G>A polymorphism is associated with PCOS risk by affecting transcriptional activity, leading to an increased expression level of Mcp-1.
Highlights
Polycystic ovary syndrome (PCOS), a very common endocrine disorder that causes up to 30% of infertility, affects 4 to 8% of the women [1,2]
Body mass index (BMI), waist/hip ratio (WHR), obesity, and hormone values were considered during PCOS diagnoses (Table 1)
dehydroepiandrosterone sulfate (DHEA-S) level was slightly higher in the PCOS patients, whereas the concentrations of luteinizing hormone (LH), T, and free T were dramatically higher in the PCOS patient group (Table 1)
Summary
Polycystic ovary syndrome (PCOS), a very common endocrine disorder that causes up to 30% of infertility, affects 4 to 8% of the women [1,2]. It is often accompanied with symptoms like ovarian dysfunction, androgen excess, obesity, and insulin resistance (IR) [1,3,4,5,6]. It is a common reproductive disease, its etiology is still not fully understood. A shared genetic background among these diseases or symptoms indicates common biological pathways underlying their etiology
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