Abstract Background Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by metabolic and reproductive disturbances. Genetic factors contribute to its pathogenesis, with polymorphisms in various genes being implicated. This study investigates the association of the rs16901946 A/G polymorphism within the PRNCR1 gene with PCOS among women in Zahedan city. Methods A case-control study was conducted involving 150 confirmed PCOS patients and 150 healthy controls from Zahedan. Genomic DNA was extracted from peripheral blood samples, and genotyping for the rs16901946 A/G polymorphism was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Statistical analyses were conducted to compare allele frequencies and genotype distributions between the two groups, adjusting for potential confounders. Results The results indicate that individuals with PCOS have significantly higher mean levels of BMI, WC, FBS, TC, and TG, whereas HDL levels are notably lower, with all differences having p-values < 0.001. However, age and LDL levels did not show significant differences between the groups. Additionally, analysis of the PRNCR1 gene polymorphism revealed significant associations with PCOS risk. Specifically, the heterozygous codominant model (p = 0.039), indicating a 2.10-fold increased risk. The homozygous codominant model had a stronger association with an OR of 5.29 (p = 0.027). In the dominant model the OR was 2.49 (p = 0.009), and in the recessive model, the OR was 4.81 (p = 0.042). Finally, the allelic model yielded an OR of 2.61 (p = 0.002). Conclusion The findings of this study suggest a significant association between the rs16901946 A/G polymorphism in the PRNCR1 gene and the susceptibility to PCOS in the Zahedan population. These results underscore the importance of genetic factors in the etiology of PCOS and may provide insights for future research and personalized treatment approaches.

Polycystic ovary syndrome (PCOS) is a complicated endocrine condition that causes ovarian dysfunction, metabolic problems, and hormonal irregularities. Genetic factors profoundly affect its pathogenesis. This study investigates the association between polymorphisms in the Transforming Growth Factor Alpha (TGFA) gene, specifically rs11466297 and rs3732248, and the risk of PCOS. We conducted a case-control study involving 200 individuals confirmed to have PCOS and 200 control subjects. We used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Amplification Refractory Mutation System (ARMS-PCR) procedures to genotype the TGFA SNPs rs11466297 A/C and rs3732248 G/A. We performed statistical analyses, including odds ratios (OR) and 95

Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder characterized by ovarian dysfunction, polycystic ovarian morphology, and hyperandrogenism. Genetic factors, including polymorphisms in microRNA (miRNAs) genes, are believed to influence its pathogenesis. This case-control study aimed to investigate the association between polymorphisms in miR-196a-2 (rs11614913), miR-146a (rs6864584), and miR-143/145 (rs41291957) and the risk of PCOS in women from Zahedan, Iran. The study comprised 286 participants: 143 women diagnosed with PCOS and 143 age-matched healthy controls. Genomic DNA was extracted from peripheral blood samples using the salting-out method. Target regions were amplified by polymerase chain reaction (PCR), and genotyping was performed by restriction fragment length polymorphism (RFLP) analysis using the enzymes MspI (rs11614913 and rs41291957) and ApaI (rs6864584). The miR-146a rs6864584 C allele significantly increased PCOS risk, with TC (OR = 2.51) and CC (OR = 2.71) genotypes conferring > 2.5-fold higher risk versus TT. Conversely, the miR-196a2 rs11614913 CT genotype showed a protective effect (42

Objectives: Type 2 diabetes (T2D) is a prevalent metabolic disorder characterized by insulin resistance and impaired glucose metabolism, often leading to severe complications. Emerging evidence suggests that exercise, particularly resistance training and aerobic activities, can significantly improve glycemic control and overall health in individuals with T2D. This study aimed to assess resistance and aerobic training, both with and without blood flow restriction (BFR), and genetic polymorphisms located in the miR-143/145 and IGF2BP2 gene clusters in men with T2D. Methods: A total of 30 men with T2D were randomly assigned to four groups: resistance training with BFR (RT-BFR), resistance training without BFR (RT), aerobic training with BFR (AT-BFR), aerobic training without BFR (AT), and two control groups. Training sessions were conducted three times per week for 12 weeks, followed by a 6-week detraining period. Genotyping was performed for polymorphisms within the miR-143/145 and IGF2BP2 gene clusters using ARMS-PCR. Results: The results of our study showed that in the AT group, the dominant genotype was TT rs4705342 TT rs4705343 GG rs4402960 AA rs1470579. In the RT group and the Control AT group, the dominant genotype was TT rs4705342 TT rs4705343 GG rs4402960 CC rs1470579. In other groups (including AT-BFR, RT-BFR, and Control RT groups), the dominant genotype was TT rs4705342 TT rs4705343 GG rs4402960 AC rs1470579.The results were significant for AT vs. Control AT at the rs4402960 position in the recessive model. Therefore, the risk decreased by 0.74 for TT vs. GT+GG (p = 0.025). Moreover, the RT group vs. Control RT group at the rs1470579 position in the same model yielded significant results, leading to a 14-fold increase in risk for CC vs. AC+AA (p < 0.001). Conclusion: The findings from this research contribute valuable evidence to the ongoing discourse surrounding exercise, genetics, and diabetes management.

Polycystic ovary syndrome (PCOS) occurs in women of reproductive age, impairing reproductive and metabolic processes. Variations in the cathepsin B (CTSB) gene can influence the disease prognosis by changing the activity, stability, or expression. These single-nucleotide polymorphisms (SNPs) can affect critical cellular functions like the deposition of extracellular matrix, inflammation, and tissue repair, leading to the development of multifactorial diseases. Our study aims to investigate the association between PCOS risk and CTSB SNPs. In this case-control study, 150 PCOS cases and 150 healthy women were enrolled. Genotyping was conducted using the PCR-RFLP method. Different computational databases were used to predict the impact of variations on the splicing sites. Regarding rs12898, the codominant homozygous (GG vs. AA) and recessive (GG vs. AA + AG) inheritance models reduced PCOS risk by 72

Objectives: Polycystic ovary syndrome (PCOS) is a multifactorial endocrinopathy characterized by various reproductive and metabolic abnormalities. The tumor suppressor p53 (TP53) plays a crucial role in cellular stress responses. Alterations in its structure or expression can influence PCOS pathogenesis. We aim to use in-silico analyses to predict the effects of the rs2287499 and rs1042522 genetic variants on the expression and structural stability of the TP53 protein. Methods: This study investigated the association of two genetic variants, rs2287499 and rs1042522, with the expression levels and folding stability of TP53 protein through in-silico analyses. Utilizing bioinformatics tools (VMD, WebLogo and PROMO), we examined the potential impacts of these variants on TP53 transcriptional activity, protein structure, and functional integrity. Results: Our findings indicate that the rs2287499 variant significantly influences TP53 expression level, while rs1042522 is associated with altered protein folding dynamics. These changes may disrupt TP53 normal regulatory functions, contributing to PCOS etiology. Furthermore, our study establishes a framework for integrating genetic variants into the understanding of TP53-mediated mechanisms in PCOS, which could pave the way for developing targeted therapeutic strategies. Conclusion: These results underscore the importance of genetic variants in PCOS hormonal and metabolic dysregulation

Type 2 diabetes mellitus (T2DM) develops primarily from obesity as leptin (LEP) functions as an essential adipokine that controls metabolic regulation, energy balance activities, and glucose maintenance. The T2DM and obesity susceptibility traits are believed to be affected by genetic variations in the leptin receptor gene (LEPR), disrupting LEP signaling mechanisms. This case-control study investigates the association of these variants with T2DM risk in a Southeastern Iranian population. A case-control study was conducted involving 450 T2DM patients and 450 matched healthy controls from Zahedan. Genomic DNA for this study was isolated from peripheral blood samples, and genotyping for the specified LEPR rs1137100, rs1137101, and rs1805094 polymorphisms was conducted using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Computational analysis created a gene-gene interaction network, highlighting LEPR as a central hub gene and detailing its interactions with related genes. Genetic models, such as codominant heterozygous (p-value = 0.009), dominant (p-value = 0.006), recessive (p-value = 0.008), and allelic (p-value = 0.011), all showed that the rs1137100 (A/G) polymorphism lowered the risk of T2DM. Several genetic models linked polymorphisms at the rs1137101 (G/A) and rs1805094 (G/C) loci to a higher risk of T2DM: The genetic models that were looked at were polymorphism rs1137101 (G/A) in codominant Homozygous (p-value = 0.031) and recessive (p-value = 0.028), as well as polymorphism rs1805094 (G/C) in codominant heterozygous (p-value = 0.009), dominant (p-value = 0.001), excess (p-value = 0.008), and allelic (p-value = 0.001). The research demonstrated a profound linkage disequilibrium (LD) among studied variants, especially in the LEPR haplotypes and across various blocks, with differing levels of association strength. The gene-gene interaction network for the LEPR gene highlights its strong associations with several key regulatory genes: LEP, PTPN11, STAT3, POMC, JAK2, IL6, and SOCS3. We found a significant correlation between LEPR gene polymorphisms and the risk of T2DM, highlighting the prominent role of genetic factors in developing such a metabolic disorder. By elucidating the association between LEPR variations and susceptibility to T2DM, our findings enhance the understanding of molecular mechanisms involved in endocrine dysregulation and highlight the importance of including genetic profiling in clinical practice.

Background:Metabolic dysfunction-associated steatotic liver disease (MASLD) is a type of fat accumulation in the liver that can lead to cirrhosis and chronic liver disease. MASLD is recognized as the most frequent of liver-associated deaths worldwide. The SERPINA1 gene encodes a serine protease protein that plays a pivotal role in the pathogenesis of liver deficiencies. In this study, we aimed to evaluate the genetic association between rs6647 (M1), rs709932 (M2), and rs1303 (M3) variants in the SERPINA1 gene and the risk of MASLD in an Iranian population. Methods:In this case-control study, 120 patients affected by MASLD and 120 healthy subjects participated. The Nephelometry system measured serum levels of α1-antitrypsin (A1AT). Biochemical tests were conducted to assess serum levels of blood parameters using commercially available kits. DNA extraction was performed using the salting-out method, followed by the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) method for genotyping. Statistical analysis was performed by SPSS v16.0. Results:The findings showed that the rs6647 G allele significantly increased the risk of MASLD. The G allele in codominant, dominant, and over-dominant models caused an increase in the risk of MASLD. Additionally, the rs709932 T allele was more frequent among patients compared to healthy subjects and significantly enhanced the risk of MASLD. The T allele in the codominant and recessive models indicated a high risk for MASLD in our population. The G allele of rs1303 caused an enhancement in the mean serum levels of A1AT in the MASLD group. Conclusions:Our results show an association between SERPINA1 gene variants and the risk of MASLD. The rs6647 (M1) and rs709932 (M2) variants of the SERPINA1 gene increased the risk of disorder in our population.

Context: Breast cancer (BC) is the most prevalent malignancy among women worldwide and represents a major public health concern. In 2020, approximately 2.3 million new cases were reported globally. Despite advances in diagnostic and therapeutic approaches, BC remains a complex disease with significant clinical and survivorship challenges. Objectives: This study aims to provide an overview of BC by summarizing its biological hallmarks, major risk factors, diagnostic approaches, treatment modalities, and the long-term needs of BC survivors. Data Sources: Relevant information was obtained from previously published scientific literature, epidemiological reports, and clinical studies addressing BC biology, diagnosis, treatment, and survivorship. Study Selection: Studies focusing on the incidence, molecular characteristics, risk factors, diagnostic methods, treatment strategies, and survivorship issues related to BC were considered. Data Extraction: Key data regarding BC hallmarks, associated risk factors, diagnostic tools, treatment options, and post-treatment needs were extracted and synthesized narratively. Results: Breast cancer is characterized by six major hallmarks, including evasion of programmed cell death, unlimited proliferative capacity, enhanced angiogenesis, resistance to growth-inhibitory signals, self-sufficiency in growth signaling, and metastatic potential. Identified risk factors include female sex, increasing age, family history, estrogen exposure, tobacco use, alcohol consumption, high-fat diet, and lifestyle factors. Diagnosis relies on physical examination, imaging techniques — particularly mammography — and tissue sampling, with image-guided core needle biopsy playing a central role. Treatment typically involves a multimodal approach combining surgery, chemotherapy (CT), radiotherapy, targeted therapy, and hormonal therapy, with more advanced disease requiring more intensive treatment. Survivors often face ongoing physical, psychological, and long-term health challenges. Conclusions: Although significant progress has been made in the diagnosis and treatment of BC, it remains a multifaceted disease requiring comprehensive management. In addition to effective therapeutic strategies, addressing the long-term physical and emotional needs of BC survivors is essential to improve overall outcomes and quality of life.

Abstract Objective Type 2 diabetes mellitus (T2DM) showed a broad etiology that both environmental and genetic factors play a role in its predisposition. Purinergic receptors have been hypothesized to be included in the pathogenicity of T2DM. The current study evaluated the association of two variants through the purinergic receptor P2X7 (P2RX7) gene with the incidence of T2DM in the population of Iran. Materials and methods We study includes 600 subjects as case and healthy groups clinically diagnosed with T2DM by clinicians referred to the diabetic clinic of Bu-Ali Hospital, Zahedan. DNA extraction followed by tetra amplification refractory mutation system polymerase chain reaction (Tetra ARMS-PCR) as a genotyping method. Results Regarding rs1718119, the codominant heterozygous (TC vs. TT), Dominant (TC + CC vs. TT), Over dominant (TC vs. TT + CC) and Allelic (C vs. T) inheritance models increased T2DM risk by 2.81, 2.94, 1.62, and 2.20 folds, respectively. Similarly, in the variant rs17525809 in the same models, the analysis showed that increased T2DM risk by 3.31, 2.56, 3.25, and 2.02 folds, respectively. Based on haplotype analysis, Crs1718119Crs17525809, Crs1718119Trs17525809 and Trs1718119Crs17525809 haplotypes significantly enhance T2DM risk by 3.97, 1.36 and 1.82 folds, respectively. Furthermore, the interaction analysis indicated that TCrs1718119/TCrs17525809, TCrs1718119/TTrs17525809 and TTrs1718119/TCrs17525809 genotype combinations strongly correlated with high T2DM risks by 7.80, 1.75 and 2.92 folds, respectively. Conclusions Our findings showed that both rs1718119T > C and rs17525809T > C increased the risk of T2DM in the Iranian population. Graphical abstract

As a multifactorial and endocrine disease, polycystic ovary syndrome (PCOS) affects approximately 5–20

Multiple investigations indicated that Silymarin (Syl), a flavonolignan extracted from the Silybum marianum plant, might possess anticancer properties. It is also advertised as a liver support dietary supplement and is accessible as a dietary supplement. Consequently, the current work sought to synthesize, describe, and analyze in vivo and in vitro the biological consequences of Syl-loaded Ni-Fe MOFs. Syl-loaded Ni-Fe MOFs were characterized by FESEM-EDAX, TEM, BET and DLS techniques, revealing their semi spherical morphology with a size range of 5-20 nm, stable particle dispersions, and mesoporous structure with a specific surface area of 74.185 m2 g-1. The encapsulation efficiency was high at 68.31 %, indicating their potential as a drug delivery system. The nanocarrier also demonstrated sustained release properties, with only 59.4 % of the drug released after 48 h, suggesting its potential for prolonged drug release to achieve therapeutic effects. Using multiple in vitro approaches such as MTT colorimetric assay and real-time PCR, we found that up -regulation of TP53 along with downregulation of mTOR was mechanistically associated with inhibition of cell growth in breast and neuroblastoma cancer cells. Treatment with Syl-loaded Ni-Fe MOFs did not result in statistically significant different liver and kidney serum parameters, whereas some histological changes were present in high -dose treated rats. On the other hand, Rats treated with three doses of free Syl showed no significant alterations in serum parameters and liver histopathology. Our results further suggest that delivering Syl to target cells via Ni-Fe MOFs could be a potential targeted approach for treating solid tumors.

Objective Type 2 diabetes mellitus (T2DM) is a complex heterogenic metabolic with a wide range of etiology. Purinergic receptors have pivotal roles in different processes and are hypothesized to have roles in the pathogenesis of T2DM. Materials and Methods Three hundred subjects affected by T2DM and 300 healthy subjects were genotyped by amplification refractory mutation system polymerase chain reaction (ARMS-PCR). SPSS V16.0 was recruited for statistical analysis. Results The findings showed that the G allele of rs25644A > G increases the risk of T2DM in our population statistically (OR = 1.51, 95% CI = 1.14-1.99, p = 0.003). This allele in some genotype models, including the dominant model, caused an increase in the risk of T2DM. The interaction of genotypes between studied variants in the P2XR4 gene increased the risk of T2DM. Haplotype analysis showed that A(rs1169727)/G(rs25644) haplotype caused an increase in the risk of T2DM. Conclusions The findings suggest that rs25644A > G plays a role in our population's increased risk of T2DM.

ABSTRACTBackgroundThe importance of long noncoding RNAs (lncRNAs) in various biological processes has been increasingly recognized in recent years. This study investigated how gene polymorphism in HOX transcript antisense RNA (HOTAIR) lncRNA affects the predisposition to chronic kidney disease (CKD).MethodsThis study comprised 150 patients with CKD and 150 healthy controls. A PCR‐RFLP and ARMS‐PCR techniques were used for genotyping the five target polymorphisms.ResultsAccording to our findings, rs4759314 confers strong protection against CKD in allelic, dominant, and codominant heterozygote genetic patterns. Furthermore, rs3816153 decreased CKD risk by 78% when TT versus GG, 55% when GG+GT versus TT, and 74% when GT versus TT+GG. In contrast, the CC+CT genotype [odds ratio (OR) = 1.66, 95% confidence intervals (CIs) = 1.05–2.63] and the T allele (OR = 1.50, 95% CI = 1.06–2.11) of rs12826786, as well as the TT genotype (OR = 2.52, 95% CI = 1.06–5.98) of rs3816153 markedly increased the risk of CKD in the Iranian population. Although no linkage disequilibrium was found between the studied variants, the Crs12826786Trs920778Grs1899663Grs4759314Grs3816153 haplotype was associated with a decreased risk of CKD by 86% (OR = 0.14, 95% CI = 0.03–0.66).ConclusionThe rs920778 was not correlated with CKD risk, whereas the HOTAIR rs4759314, rs12826786, rs1899663, and rs3816153 polymorphisms affected the risk of CKD in our population. It seems essential to conduct repeated studies across various ethnic groups to explore the link between HOTAIR variants and their impact on the disease outcome.

Polycyclic aromatic hydrocarbons (PAHs) are a class of hydrocarbons, some of which are established human carcinogens. Human exposure to these chemicals is complex and originates from both indoor and outdoor sources. This study measured the concentration of PAHs in the gaseous and particulate phases during the cold months of 2022 using XAD-2 sorbent tubes and Polytetrafluoroethylene (PTFE) filters in the indoor air of coffee shops in Zahedan, Iran (n=23). The average concentrations of particulate-bound PAHs and gaseous PAHs were 13,411.86 ± 6,517.24 ng/m³ and 6,432.76 ± 4,311.72 ng/m³, respectively. Source apportionment analyses indicated that the primary sources of PAHs in coffee shops were fossil fuel combustion and environmental tobacco smoke (ETS), commonly referred to as second and third-hand smoke. The lifetime cancer risk (LTCR) of inhaled PAHs was calculated using the Monte Carlo simulation method. The mean LTCR for adults and children from inhaling these substances were 9.43×10 - 6 ± 5.06 ×10 - 6 and 5.34×10 - 6 ± 2.87 ×10 - 6, respectively. The hazard quotient (HQ) of PAHs exceeded 1. These findings highlight the need to reduce PAHs exposure in public spaces through proper health warning labels and regulated indoor smoking policies.

Diabetes, a leading cause of death globally, has different types, with Type 2 Diabetes Mellitus (T2DM) being the most prevalent one. It has been established that variations in the SLC11A1 gene impact risk of developing infectious, inflammatory, and endocrine disorders. This study is aimed to investigate the association between the SLC11A1 gene polymorphisms (rs3731864 G/A, rs3731865 C/G, and rs17235416 + TGTG/− TGTG) and anthropometric and biochemical parameters describing T2DM. Eight hundred participants (400 in each case and control group) were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) and amplification-refractory mutation system-PCR (ARMS-PCR) methods. Lipid profile, fasting blood sugar (FBS), hemoglobin A1c level, and anthropometric indices were also recorded for each subject. Findings revealed that SLC11A1 –rs3731864 G/A, –rs17235416 (+ TGTG/− TGTG) were associated with T2DM susceptibility, providing protection against the disease. In contrast, SLC11A1 –rs3731865 G/C conferred an increased risk of T2DM. We also noticed a significant association between SLC11A1 –rs3731864 G/A and triglyceride levels in patients with T2DM. In silico evaluations demonstrated that the SLC11A2 and ATP7A proteins also interact directly with the SLC11A1 protein in Homo sapiens . In addition, allelic substitutions for both intronic variants disrupt or create binding sites for splicing factors and serve a functional effect. Overall, our findings highlighted the role of SLC11A1 gene variations might have positive (rs3731865 G/C) or negative (rs3731864 G/A and rs17235416 + TGTG/− TGTG) associations with a predisposition to T2DM.

Introduction: The two main causes of indoor air pollution (IAP) are cooking and smoking. Toxic substances, including polycyclic aromatic hydrocarbons (PAHs), recognized as human carcinogens, are present in cooking and tobacco smoke. This study aims to determine the cytotoxicity and genotoxicity of PAHs collected from the indoor air of coffee shops on human cell line (KB/C152) in vitro approach. Materials and methods: Sampling pumps at a 2 l/min flow rate for 5 hours were applied to collect indoor air samples. Next, KB cells in cell culture medium were exposed to different concentrations of extracted PAHs using Methyl Thiazolyl Tetrazolium (MTT) test. Finally, terminal dUTP nick-end labeling (TUNEL) test and cell cycle assessments were both examined using flow cytometry. Results: The MTT test revealed a significant cytotoxic effect on KB cells depending on the PAHs concentrationas compared to the control cell line. The lethal concentration 50 (LC50) value against KB cells was 100 ± 3.09 µg/ml. Accordingly, exposure to extracted PAHs resulted in an arrest in the cell cycle at the sub-G1 checkpoint. The extracted PAHs suppressed the cell cycle in the sub-G1 phase, damaged DNA, and arrested KB cells from proliferating. Additionally, a statistically significant increase in DNA cleavage percentages (p ≤ 0.05) was seen in the TUNEL test, which also showed a dose-dependent increase in DNA damage. Conclusion: Extracted PAHs caused DNA damage and arrested in the cell cycle in epidermoid carcinoma of the mouth cells (KB/C152) in vitro mechanisms. This evaluation highlights mechanisms of exposure to extracted PAHs and their detrimental health effects.

Background:This study aimed to compare the effects of laser photodynamic therapy (PDT) with methylene blue (MB) or aminolevulinic acid (ALA) on the oral squamous cell carcinoma (OSCC) cell line.Materials and Methods:In this in vitro experimental study, the C152 (KB) OSCC cell line was cultured in a culture medium containing 10% fetal bovine serum. The cells were exposed to 0.1, 0.2, 0.5, 1, 2, 5, and 10 mM concentrations of MB and ALA alone and combined with diode laser irradiation with 660 nm wavelength, 40 mW power, and 10 J/cm2 energy density in continuous-wave mode perpendicular to the surface. Cell viability was assessed using the methyl thiazolyl tetrazolium assay and compared among the groups by the Kruskal-Wallis test.Results:The results showed that the reduction in cell viability in the MB + laser and ALA + laser groups was greater than that in the MB and ALA groups without laser (P < 0.001). Significant differences were noted in cell viability in the presence of some different concentrations of MB and ALA (P < 0.05), such that by an increase in their concentration, cell viability decreased. Cell viability in the MB + laser group was significantly lower than that in the ALA + laser group in some photosensitizer concentrations (P < 0.05).Conclusion:Within the limitations of this in vitro study, the results showed that laser PDT with MB (high concentrations) was more effective than laser PDT with ALA against the OSCC cell line.

Polycystic ovarian syndrome (PCOS) is a complex endocrine and metabolic condition with several potential causes. Insulin resistance is a hallmark of PCOS that often coexists with hirsutism, hyperandrogenism, being overweight, and hormonal imbalances. The functioning of multiple replication and transcription factors is regulated by tumor suppressor genes (TSGs), which play a crucial role in maintaining genomic integrity and controlling the cell cycle of granulosa cells. In the present study, we examined how three single nucleotide polymorphisms (SNPs) in TP53, a cell cycle regulatory gene, affect the risk of developing PCOS in a sample of an Iranian population. Genomic DNA was extracted from 200 PCOS patients and 200 healthy women to analyze TP53 rs17880604, rs1625895, and rs1042522 SNPs using the polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) method. Our findings revealed that the majority of PCOS cases were overweight [25 < body mass index (BMI) < 30]. A positive association was observed between the TP53 rs1042522 SNP and the risk of PCOS under codominant heterozygous and overdominant genetic patterns (odds ratio > 1). Meanwhile, a negative association was observed between TP53 SNPs (rs1625895, rs17880604) and susceptibility to PCOS under codominant heterozygous and dominant models of inheritance (odds ratio < 1). Moreover, different genotype and haplotype combinations of rs17880604/rs1625895/rs1042522 conferred a decreased risk of PCOS in our population. We found no statistical difference in the frequency of TP53 genotypes between PCOS cases and/or controls in terms of BMI, waist circumference, prolactin level, and markers of lipid and carbohydrate profile (P > 0.05). Molecular dynamic prediction showed that the missense substitution in the 17p13.1 position (rs1042522) could change the properties and secondary structure of the p53 protein. As inherited risk factors, TP53 variations may play a pivotal role in the pathogenesis of PCOS among Iranian women. Replicated population-based studies on other ethnicities are required to find the genetic contribution of variants of TP53, or SNPs located in other TSGs, to the etiology of this endocrine disease.

Polycystic ovary syndrome (PCOS) is known as a multifactorial and multi-gene-mediated endocrine disorder among women of reproductive age. FoxO1 and FoxO3 are members of the forkhead transcriptional factors family that play a pivotal role in the function of ovaries. The current work is aimed at investigating the association between gene variants of FoxO1 and FoxO3 and the risk of PCOS in a sample of the Iranian population. We recruited 200 women diagnosed with PCOS and 200 healthy women. Both polymerase PCR–RFLP and ARMS-PCR methods were used for genotyping. Sanger sequencing was recruited to confirm the genotyping results. The T allele of rs17592236 and the C allele of rs12585277 decreased PCOS risk by 29 and 28