Abstract
<title>Abstract</title> <p>Background Polycystic ovary syndrome (PCOS) is a complex endocrine disorder with a polygenic etiology. Although luteinizing hormone/chorionic gonadotropin receptor (LHCGR) gene variants influence PCOS susceptibility globally, data on the Iraqi population remain absent. Objective To evaluate the association between the LHCGR rs2293275 polymorphism and PCOS clinical symptoms, including hirsutism, menstrual irregularities, and reproductive hormones, in Iraqi women. Methodology : A case-control study included 100 PCOS women (Rotterdam 2003 criteria) and 50 age-matched healthy controls. Clinical, anthropometric, and hormonal (FSH, LH, PRL, E2, testosterone, AMH) assessments were performed. Genomic DNA was extracted, and the rs2293275 variant was genotyped using PCR and Sanger sequencing in a subset (32 patients, 31 controls). Results PCOS patients exhibited significantly higher BMI, testosterone, AMH, and LH/FSH ratios compared to controls (p < 0.05). The rs2293275 GG genotype was significantly more frequent in PCOS patients (50%) than controls (23%), increasing PCOS risk 7.5-fold (OR = 7.5, 95% CI: 1.78–31.04; p = 0.004). The G allele was an independent risk factor (OR = 3.3, p = 0.002). Furthermore, the GG genotype was associated with significantly elevated AMH levels (p = 0.002), which strongly predicted menstrual irregularity (p < 0.001). A novel synonymous variant (c.805T > C) was also identified upstream of rs2293275. Conclusion The LHCGR rs2293275 GG genotype and G allele are significant risk factors for PCOS in Iraqi women, strongly correlating with elevated AMH levels. This genetic variant may mechanistically contribute to the follicular arrest and anovulatory phenotypes observed in this population, highlighting its potential as a molecular risk marker.</p>