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

Syed Douhath Yousuf; Mohammad Ashraf Ganie; Syed Mudassar; Humiara Shafi; Saima Ibrahim; Humira Jeelani; Gowhar Rashid; Mohammad A Zargar; Fouzia Rashid

doi:10.4103/jfmpc.jfmpc_1916_21

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

J Family Med Prim Care. 2022 Aug;11(8):4743-4752. doi: 10.4103/jfmpc.jfmpc_1916_21. Epub 2022 Aug 30.

Authors

Syed Douhath Yousuf¹, Mohammad Ashraf Ganie², Syed Mudassar¹, Humiara Shafi³, Saima Ibrahim³, Humira Jeelani⁴, Gowhar Rashid¹, Mohammad A Zargar⁵, Fouzia Rashid³

Affiliations

¹ Department of Clinical Biochemistry, Sher-i-Kashmir Institute of Medical Sciences (SKIMS), Jammu and Kashmir, India.
² Department of Endocinology, Sher-i-Kashmir Institute of Medical Sciences (SKIMS), Jammu and Kashmir, India.
³ Department of Clinical Biochemistry, University of Kashmir, Jammu and Kashmir, India.
⁴ Advanced Centre for Human Genetics, Sher-i-Kashmir Institute of Medical Sciences (SKIMS), Jammu and Kashmir, India.
⁵ Department of Biotechnology, Nuner Campus, Central University of Kashmir, Jammu and Kashmir, India.

Abstract

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.

Keywords: Coagulation; inflammation; monocyte chemoattractant protein-1; plasminogen activator inhibitor-1; polycystic ovary syndrome; polymorphism.