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.

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; P = 0.001), whereas the OR for the 4G/5G genotype was (OR = 2.39; P = 0.001). The carriers with the 4G/4G and 4G/5G genotypes showed significantly increasing trends in the triglyceride levels ( P < 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; P = 0.01) and the AG genotype (OR = 2.40; P = 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 ( P < 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.