{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T22:49:11Z","timestamp":1792190951003,"version":"4.4.0"},"reference-count":53,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T00:00:00Z","timestamp":1743206400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research, Development, and Innovation Authority (RDIA), Saudi Arabia, Riyadh, Reactivating &amp; Rebuilding of Existing Labs Initiative","award":["13262-Tabuk-2023-UT-R-3\u20131-HW"],"award-info":[{"award-number":["13262-Tabuk-2023-UT-R-3\u20131-HW"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Background: As a complicated endocrine condition, polycystic ovarian syndrome affects around 20% of women who are of reproductive age. It is linked to an increased risk of endometrial cancer, cardiovascular diseases, mental illnesses, non-alcoholic fatty liver disease, metabolic syndrome, and Type 2 diabetes. Despite numerous genetic studies identifying several susceptibility loci, these only account for approximately 10% of the hereditary factors contributing to PCOS, leaving its etiology largely unknown. While genome-wide association studies (GWAS) have been conducted on various populations to identify SNPs linked to PCOS risk, no such study has been reported in Tabuk. Thus, this study aims to investigate the association of a glutathione S-transferase M1 (GSTM1) deletion, VEGF gene (I\/D) insertion\/deletion, and VEGF-2578 gene polymorphism with polycystic ovarian syndrome. Methodology: In this research study (case-control), we utilized the ARMS-PCR to determine and analyze the polymorphic variants of VEGF-2578 C\/A (rs699947). We employed multiplex PCR for the GSTM1 deletion and MS-PCR (mutation specific PCR) for the vascular endothelial growth factor gene insertion\/deletion. Results: The findings indicated statistically significant differences in various biochemical and endocrine serum biomarkers, including lipid profiles (cholesterol, HDL, and LDL), Type 2 diabetes markers (HOMA-IR (Homeostatic Model Assessment for Insulin Resistance), free insulin fasting glucose), and hormone levels (testosterone, LH, progesterone and FSH) in PCOS patients. Specifically, regarding the GSTT1 genotype, individuals with the GSTT1-null genotype had an odds ratio (OR) of 4.16 and a relative risk (RR) of 2.14 compared to those with the GSTT1 genotype, with statistically significant differences (p = 0.0001). However, for the GSTM1 genotype, there was a statistically significant difference (p = 0.0002) in the OR and RR for the GSTM1-null genotype, which were 2.66 and 1.64, respectively. Protective effects were observed for individuals with either GSTT1 (+) GSTM1 (\u2212) or GSTT1 (\u2212) GSTM1 (+) genotypes, as well as for those with both null genotypes, yielding an OR of 0.41 and p &lt; 0.003. The VEGF rs699947 C&gt;A gene variation showed a statistically significant association between PCOS patients and controls (p &lt; 0.020), with the A allele frequency higher among PCOS patients (0.42 vs. 0.30). Similarly, the VEGF rs4646994 I&gt;D gene variation exhibited a statistically significant difference (p &lt; 0.0034), with the D allele being more frequent in PCOS patients (0.52 vs. 0.35). The VEGF-A allele was strongly linked to PCOS susceptibility in the allelic model, exhibiting an OR of 1.62, RR of 1.27, and p &lt; 0.007, while in the allelic comparison, the OR was 1.71, the RR was 1.32, and p &lt; 0.004. Conclusions: This study concluded that null genotypes at rs4025935 and rs71748309, an insertion deletion at rs4646994, and the A allele of rs699947 were significantly associated with PCOS predisposition in our population and these could serve as potential loci for PCOS predisposition. To the best of our knowledge, it is the first study to highlight the association between these genetic variations and the predisposition of PCOS in our populations. Large-scale case-control studies in the future are required to confirm these results.<\/jats:p>","DOI":"10.3390\/life15040558","type":"journal-article","created":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T05:21:04Z","timestamp":1743398464000},"page":"558","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Evaluating the Impact of rs4025935, rs71748309, rs699947, and rs4646994 Genetic Determinants on Polycystic Ovary Syndrome Predisposition\u2014A Case-Control Study"],"prefix":"10.3390","volume":"15","author":[{"given":"Reema","family":"Almotairi","sequence":"first","affiliation":[{"name":"Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Prince Fahad Bin Sultan Chair for Biomedical Research, University of Tabuk, Tabuk 71491, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashid","family":"Mir","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Prince Fahad Bin Sultan Chair for Biomedical Research, University of Tabuk, Tabuk 71491, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kholoud S.","family":"Almasoudi","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Prince Fahad Bin Sultan Chair for Biomedical Research, University of Tabuk, Tabuk 71491, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eram","family":"Husain","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Prince Fahad Bin Sultan Chair for Biomedical Research, University of Tabuk, Tabuk 71491, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4113-3945","authenticated-orcid":false,"given":"Nabil","family":"Mtiraoui","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genome and Multifactorial Diseases, Faculty of Pharmacy, University of Monastir, Monastir 5000, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S0002-9378(15)30642-6","article-title":"Amenorrhea associated with bilateral polycystic ovaries","volume":"29","author":"Stein","year":"1935","journal-title":"Am. 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