Using ChatGPT to predict the future of personalized medicine.

Personalized medicine is a novel frontier in health care that is based on each person's unique genetic makeup. It represents an exciting opportunity to improve the future of individualized health care for all individuals. Pharmacogenomics, as the main part of personalized medicine, aims to optimize and create a more targeted treatment approach based on genetic variations in drug response. It is predicted that future treatments will be algorithm-based instead of evidence-based that will consider a patient's genetic, transcriptomic, proteomic, epigenetic, and lifestyle factors resulting in individualized medication. A generative pretrained transformer (GPT) is an artificial intelligence (AI) tool that generates language resembling human-like writing enabling users to engage in a manner that is practically identical to speaking with a human being. GPT's predictive algorithms can respond to questions that have never been addressed. Chat Generative Pretrained Transformer (ChatGPT) is an AI chatbot's advanced with conversational capabilities. In the present study, questions were asked from ChatGPT about the future of personalized medicine and pharmacogenomics. ChatGPT predicted both to be a promising approach with a bright future that holds great promises in improving patient outcomes and transforming the field of medicine. But it still has several limitations that need to be solved.

Breast cancer in the era of precision medicine.

Breast cancer is a heterogeneous disorder with different molecular subtypes and biological characteristics for which there are diverse therapeutic approaches and clinical outcomes specific to any molecular subtype. It is a global health concern due to a lack of efficient therapy regimens that might be used for all disease subtypes. Therefore, treatment customization for each patient depending on molecular characteristics should be considered. Precision medicine for breast cancer is an approach to diagnosis, treatment, and prevention of the disease that takes into consideration the patient's genetic makeup. Precision medicine provides the promise of highly individualized treatment, in which each individual breast cancer patient receives the most appropriate diagnostics and targeted therapies based on the genetic profile of cancer. The knowledge about the molecular features and development of breast cancer treatment approaches has increased, which led to the development of new targeted therapeutics. Tumor genomic profiling is the standard of care for breast cancer that could contribute to taking steps to better management of malignancies. It holds great promise for accurate prognostication, prediction of response to common systemic therapies, and individualized monitoring of the disease. The emergence of targeted treatment has significantly enhanced the survival of patients with breast cancer and contributed to reducing the economic costs of the health system. In this review, we summarized the therapeutic approaches associated with the molecular classification of breast cancer to help the best treatment selection specific to the target patient.

Precision medicine journey through omics approach.

It has been well established that understanding the underlying heterogeneity of numerous complex disease process needs new strategies that present in precision medicine for prediction, prevention and personalized treatment strategies. This approach must be tailored for each individual's unique omics that lead to personalized management of disease. The correlation between different omics data should be considered in precision medicine approach. The interaction provides a hypothesis which is called domino effect in the present minireview. Here we review the various potentials of omics data including genomics, transcriptomics, proteomics, metabolomics, pharmacogenomics. We comprehensively summarize the impact of omics data and its major role in precision medicine and provide a description about the domino effect on the pathophysiology of diseases. Each constituent of the omics data typically provides different information in associated with disease. Current research, although inadequate, clearly indicate that the information of omics data can be applicable in the concept of precision medicine. Integration of different omics data type in domino effect hypothesis can explain the causative changes of disease as it is discussed in the system biology too. While most existing studies investigate the omics data separately, data integration is needed on the horizon of precision medicine by using machine learning.

Genomic medicine on the frontier of precision medicine.

Genomic medicine has created a great deal of hope since the completion of the Human Genome Project (HGP). Genomic medicine promises disease prevention and early diagnosis in the context of precision medicine. Precision medicine as a scientific discipline has introduced as an evolution in medicine. The rapid growth of high-development technologies permits the assessment of biological systems. Study of the integrated profiles of omics, such as genome, transcriptome, proteome and other omics information lead to significant advances in personalized and precision medicine. In the context of precision medicine, pharmacogenomics can play an important role in order to discriminate responders and non-responders to medications and avoiding toxicity and achieving the optimum dose. So precision medicine in accordance with genomic medicine will transform medicine from conventional evidence-based medicine in the diagnosis and treatment towards precision based-medicine. In this review, we have summarized the related issues for genomic medicine and precision medicine.

Artificial intelligence perspective in the future of endocrine diseases.

In recent years, artificial intelligence (AI) shows promising results in the diagnosis, prediction, and management of diseases. The move from handwritten medical notes to electronic health records and a huge number of digital data commenced in the era of big data in medicine. AI can improve physician performance and help better clinical decision making which is called augmented intelligence. The methods applied in the research of AI and endocrinology include machine learning, artificial neural networks, and natural language processing. Current research in AI technology is making major efforts to improve decision support systems for patient use. One of the best-known applications of AI in endocrinology was seen in diabetes management, which includes prediction, diagnosis of diabetes complications (measuring microalbuminuria, retinopathy), and glycemic control. AI-related technologies are being found to assist in the diagnosis of other endocrine diseases such as thyroid cancer and osteoporosis. This review attempts to provide insight for the development of prospective for AI with a focus on endocrinology.

Influence of cytotoxic T lymphocyte antigen 4 genetic variants on acute rejection in kidney transplant patients: precision medicine perspective.

Background: The most effective and common treatment for end-stage renal disease is kidney transplantation.The personalized approach to kidney transplantation, which utilizes precision medicine principles, determines distinctive genomics characteristics of candidates/recipients that must be taken into account. Cytotoxic T lymphocyte associated protein 4 (CTLA4) may be a suitable candidate gene for studying allograft rejection. The aim of this study was to understand whether we can consider two common variants of the CTLA4 gene as a risk factor of transplant rejection in a group of Iranian population. Methods: Totally, 169 kidney transplant recipients, including acute rejections (N=39) and non-rejection (N=130) groups who underwent transplantation were included in this study. The genotyping of rs5742909 (-318C/T) and rs231775 (+49A/G) variants of the CTLA4 gene were performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Results: The AG genotype frequency of rs231775 variant was the same in both patients with and without a history of rejection while, none of those groups had homozygote genotype. In rs5742909, both CT and TT frequencies of patients with rejected transplant were lower than patients with a normal outcome. Conclusions: The results of the presented study suggest that rs231775 and rs5742909 of CTLA4 genetic variants are not linked to acute rejection who underwent kidney transplantation. So, these variants cannot be considered as risk factors of acute allograft rejection in a group of Iranian renal transplantation recipients. However, the transplantation precision medicine may be an important area for the improvement of patients outcome as the precision medicine has already entered clinical practice in kidney transplantation.

Effects of the TCF7L2 and KCNQ1 common variant on sulfonylurea response in type 2 diabetes mellitus patients: a preliminary pharmacogenetic study.

Background: Type 2 diabetes mellitus (T2DM) is a common chronic condition characterized by high blood glucose levels which is caused by genetic and environmental factors. Currently, pharmacogenomics (PGx) is anticipated to enable the development of personalized treatment in a wide range of health issues. Sulfonylureas (SFUs) are among the oral anti-diabetic drugs that are very popular due to their low cost. Genetic variants in transcription factor 7 like 2 (TCF7L2) and potassium voltage-gated channel subfamily Q member 1 (KCNQ1) have been reported for altered therapeutic response to sulfonylurea. The aim of the present study is to evaluate any association between common genetic variant of the TCF7L2 and KCNQ1 (rs7903146 and rs2237892, respectively) and the response to sulfonylurea in a group of Iranian patients for the first time. Methods: Genotyping was carried out in 30 T2DM patients who received sulfonylurea treatment for more than two months in addition to previous medication using the Sanger sequencing method. Results: In 30 T2DM patients who received SFUs treatment, 60%, 33.3% and 6.7% had CC, CT and TT genotypes, respectively. After treatment, adjusted fasting blood sugar (FBS) mean reduction level in CT and TT carriers was lower than CC carriers. Adjusted hemoglobin A1c (HbA1c) mean reduction level was also lower in CT and TT compared with CC carriers, but, none of these differences were statistically significant. Genotype frequencies of TT, CT and CC genotypes of rs2237892 variant of KCNQ1 gene were 0 (0%), 3 (10%) and 27 (90%) respectively. Patients with CT and CC genotypes of rs2237892 variant had also similar changes in FBS (P=0.200) and HbA1c (P=0.436) after treatment with SFUs. Conclusions: Genotypes of TCF7L2 and KCNQ1 common variant did not show any impact on the treatment response among T2DM patients receiving SFUs.

The role of the PPARG (Pro12Ala) common genetic variant on type 2 diabetes mellitus risk.

BACKGROUND: Type 2 diabetes (T2DM) prevalence has been rapidly increasing in the last decades. T2DM pathogenesis is related to insulin resistance and beta-cell dysfunction. Peroxisome proliferator-activated receptor gamma (PPARG) is concerned about T2DM risk through the involvement in adipocyte differentiation and energy homeostasis. The present study aimed to find the risk associated with a common genetic variant (Pro12Ala) of the PPARG gene in the development of T2DM in a group of the Iranian population. METHODS: Totally, 149 patients with T2DM and 96 healthy individuals were recruited in this case-control study. The genotyping of the genetic variant was carried out using the polymerase chain reaction (PCR) followed by Sanger sequencing. RESULTS: No significant difference is observed between the CG and GG genotypes frequency of the PPARG variant (P = 0.17) in T2DM patient and the control groups. Furthermore, the frequency of the G allele was similar between case and control groups. The Pro12Ala variant may decrease the risk of diabetic retinopathy (DR) which was not statistically significant. Furthermore, the Pro12Ala variant caused a 27% increase in the risk of diabetes nephropathy (DN) among patients with T2DM but was not significant. CONCLUSIONS: Our findings showed that the PPARG variant could not impact on T2DM development and its complications.

A systematic review of miRNAs as biomarkers in osteoporosis disease.

BACKGROUND: Osteoporosis is often considered to be a disease of the elderly, which is characterized by two characteristics: low bone mineral density (BMD) and increased risk of fracture. MicroRNAs (miRNAs) have been reported to play a potential role in bone formation and resorption, bone remodeling, bone homeostasis regulation, and bone cell differentiation. Therefore, altered expression of different miRNAs may impact the pathology of bone diseases such as osteoporosis. A systematic review was conducted to extract all miRNA found to be significantly dys-regulated in the peripheral blood. METHODS: This review was carried out using a systematically search on PubMed, Scopus, Embase, Web of Science (WoS), and Cochrane databases from 1990 to 2018 to explore the diagnostic value of miRNAs as a biomarker in osteoporosis. RESULTS: A total of 31 studies were identified in the systematic review that indicated more than 30 kinds of up-regulated and down-regulated miRNAs in three categories; postmenopausal osteoporosis, postmenopausal osteoporosis with fracture risk, and other types of osteoporosis and fracture risk. CONCLUSION: The collective data presented in this review indicate that miRNAs could serve as biomarkers for the diagnosis (onset) and prognosis (progression of osteoporosis), while the clinical application of these findings has yet to be verified. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-021-00873-5.

Pilot study in pharmacogenomic management of empagliflozin in type 2 diabetes mellitus patients.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a metabolic disorder in which the patients with high blood sugar develop insufficient insulin secretion or insulin resistance. The solute carrier family, 5 member 2 (SLC5A2) gene is a member of sodium/glucose transporter family which can reduce heart and kidney problems. The current study aims to look into any association between rs11646054 variant in SLC5A2 gene and the anti-diabetic efficacy and safety of empagliflozin. METHODS: 14 T2DM who failed to respond to previous treatments, empagliflozin 10 mg was added for 6 months. Genotyping of the rs11646054 variant of SLC5A2 gene was performed by polymerase chain reaction (PCR) followed by Sanger sequencing. RESULTS: Although hemoglobin A1c (HbA1c) and low-density lipoprotein (LDL) were not significantly different, but the mean fasting blood sugar (FBS), 2-h post prandial (2hpp), albumin-to-creatinine ratio (ACR), and total cholesterol (TC) were significantly decreased after 6 months empagliflozin treatment. There was a significant difference in the mean final reductions in FBS level among genotypes. It's important to mention that those who were GG homozygotes had a tendency to have more decrements. CONCLUSIONS: The study results indicate that effects of variation in SLC5A2 (rs11646054) on the clinical efficacy of empagliflozin were negligible.

A pharmacogenetic pilot study of CYP2C9 common genetic variant and sulfonylureas therapeutic response in type 2 diabetes mellitus patients.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease that is associated with elevated blood glucose levels. Sulfonylureas (SFUs) are the most widely used among the oral antidiabetic drugs that are highly metabolized by cytochrome P450 family 2 subfamily C member 9 (CYP2C9). The CYP2C9 has been shown to be associated with a better glycemic response to SFUs and a lower treatment failure rate. The aim of the present study was to assess the influence of the CYP2C9 rs1067910 gene variant on the SFUs response in a group of Iranian patients for the first time. METHODS: Blood samples were taken from 30 patients with T2DM under sulfonylurea treatment. DNA extraction was performed using Salting out method, and then genotyping was performed by polymerase chain reaction (PCR) followed by Sanger sequencing. RESULTS: There was no significant difference in the fasting blood sugar (FBS) between T2DM patients with different genotypes before and after the treatment with SFUs (P = 0.073 and P = 0.893, respectively). Although HbA1c was significantly different among AA, CA and CC carriers before (P = 0.001) and after (P = 0.018) treatment, no significant change was observed after treatment in all three groups. CONCLUSIONS: In the present study based on only 30 samples in pilot survey, it is shown that the therapeutic response to SFUs was not related to rs1057910 CYP2C9 variant.

Investigation of TGF-ß1 gene variant and expression in a group of Iranian women with endometriosis.

PURPOSE: Endometriosis is defined as a common gynecologic and inflammatory disease. Transforming growth factor-beta 1 (TGF-ß1) gene and its protein level might play a role in the pathogenesis of endometriosis. The present study aimed for the first time to assess the associations between endometriosis risk and - 509 C/T (rs1800469) variant of the TGF-ß1 gene as well as TGF-ß1 mRNA expression in eutopic endometrium tissue of patients with and without endometriosis among a group of Iranian women. METHODS: Genotyping was carried out in 100 endometriosis patients (cases) with confirmed histological diagnosis of endometriosis and 197 non-endometriosis subjects (controls). The expression level of TGF-ß1 mRNA was determined using Real-Time PCR assay in 15 eutopic endometrium tissue of women with endometriosis and 15 healthy controls. RESULTS: There was a significant association for allele and genotype frequencies of rs1800469 variant and endometriosis. No significant difference for TGF-ß1 expression was observed between eutopic endometrium of patients and healthy group. Also, evaluation of TGF-ß1expression across the menstrual cycle showed the same level of TGF-ß1 among case and control subjects. CONCLUSION: Our investigations indicated enough evidence for the effect of TGF-ß1 genetic variant on endometriosis risk in an Iranian population. Furthermore, we could not find any relations between TGF-ß1 mRNA expression and susceptibility to endometriosis.

Investigating the association of matrix metalloproteinase-2 gene variants with endometriosis in an Iranian population.

OBJECTIVES: matrix metalloproteinases including matrix metalloproteinase-2 play a key role in endometrial extra cellular matrix breakdown in endometriosis. Aberrant expression of matrix metalloproteinase-2 has been reported in eutopic and ectopic endometrial tissue of endometriosis patients so altered expression of matrix metalloproteinase-2 due to polymorphisms may lead to establishment and progression of endometriosis. In this study the association between -735 C/T (rs2285053) and -1575 G/A (rs243866) variants of matrix metalloproteinase-2 gene with presence of endometriosis in an Iranian population were investigated for the first time. STUDY DESIGN: A case-control association study was conducted to investigate the role of MMP-2-735 C/T and _1575 G/A variants in development of endometriosis. Polymerase chain reaction-restriction fragment length polymorphism method was used to determine genotype frequencies of these variants in 100 endometriosis patients and 200 normal samples. Total genomic DNA was extracted from blood samples and single-nucleotide polymorphism flanking regions were amplified using designed specific primers. Enzymatic digestion was performed using Pag I and Hinf I restriction enzymes for rs2285053 and rs243866 variants, respectively. Statistical analysis was ascertained using statistical package for social science version 16 and "SHEsis" software. RESULTS: There were no significant differences in genotype frequencies of rs2285035 (-735C/T) variant between case and control groups (CC + CT vs. TT p = 0.40; OR = 0.50, 95 % CI 0.100-2.551). There were also no significant differences for C allele frequencies in both case and control groups (p = 0.9). For variant rs243866 (-1575 G/A) the differences in genotype frequencies between case and controls group were determined to be significant (GG + GA vs. AA p = 0.041; OR = 6.46, 95 % CI 0.82-50.43). The frequency of G allele was significantly different in case and control groups (p = 0.037). CONCLUSION: In conclusion, existence of rs243866 variant in promoter region of matrix metalloproteinase-2 gene can increase the risk of endometriosis in Iranian women.

PPARG (Pro12Ala) genetic variant and risk of T2DM: a systematic review and meta-analysis.

Type 2 diabetes mellitus (T2DM) is a complex disease caused by the interaction between genetic and environmental factors. A growing number of evidence suggests that the peroxisome proliferator-activated receptor gamma (PPARG) gene plays a major role in T2DM development. Meta-analysis of genetic association studies is an efficient tool to gain a better understanding of multifactorial diseases and potentially to provide valuable insights into gene-disease interactions. The present study was focused on assessing the association between Pro12Ala variation in the PPARG and T2DM risk through a comprehensive meta-analysis. We searched PubMed, WoS, Embase, Scopus and ProQuest from 1990 to 2017. The fixed-effect or random-effect model was used to evaluate the pooled odds ratios (ORs) and 95% confidence intervals (CIs) depending on the heterogeneity among studies. The sources of heterogeneity and publication bias among the included studies were assessed using I2 statistics and Egger's tests. A total of 73 studies, involving 62,250 cases and 69,613 controls were included. The results showed that the minor allele (G) of the rs1801282 variant was associated with the decreased risk of T2DM under different genetic models. Moreover, the protective effect of minor allele was detected to be significantly more in some ethnicities including the European (18%), East Asian (20%), and South East Asian (18%). And the reduction of T2DM risk in Ala12 carriers was stronger in individuals from North Europe rather than Central and South Europe. Our findings indicated that the rs1801282 variant may contribute to decrease of T2DM susceptibility in different ancestries.

KCNQ1 common genetic variant and type 2 diabetes mellitus risk.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a multifactorial trait that both environmental and genetic factors contribute to its pathogenesis. The most common single nucleotide polymorphism (SNP) of the potassium voltage-gated channel subfamily Q member 1 (KCNQ1) gene, rs2237892, is highly associated with the risk of T2DM. The aim of the present study was to examine any association between KCNQ1 gene rs2237892 variant and risk of T2DM in a group of Iranian patients. METHODS: Genotyping was carried out in 100 type 2 diabetic patients and 100 non-diabetic subjects using the Sanger sequencing method. RESULTS: The CC genotype caused more than 30% reduction in the risk of T2DM in compared with CT. Nonetheless, this association was not statistically significant and this variant had no protective effect for T2DM. A significant difference was not found in genotypes (CC, CT, and TT) and alleles (C and T) frequency of KCNQ1 rs2237892 SNP between T2DM and control groups (P = 0.475 and P = 0.470, respectively). CONCLUSIONS: Our investigations did not show enough evidence for the presence of an association between KCNQ1 gene rs2237892 polymorphism and risk of T2DM among a group of Iranian patients.

Genetic Polymorphism of Mismatch Repair Genes and Susceptibility to Prostate Cancer.

PURPOSE: Mismatch repair (MMR) is one of the DNA repair systems that correct mispaired bases during DNA replication errors. Polymorphisms in genes can increase susceptibility to the development of prostate cancer (PCa). In this study, we investigated mutL homolog 1 (MLH1) -93G>A (rs1800734) and mutS homolog 3 (MSH3) (rs26279) polymorphisms with the risk of PCa. MATERIALS AND METHODS: In this study of Iranian population, 175 histopathologically confirmed (PCa) patients and 230 benign prostate hyperplasia (BPH) as the controls were recruited. The genotypes of MLH1 and MSH3 were determined by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: There was no significant difference of MLH1 (P = 0.4) and MSH3 (P?=?0.5) genotype distributions among PCa cases and controls. And also patients with PCa were not significant differences compared to those without in stage of cancer, grade of tumor, perineural invasion, and vascular invasion. CONCLUSION: Our results did not show adequate evidence for any significant association of MLH1 and MSH3 polymorphisms and PCa .

Gut microbiota: a perspective of precision medicine in endocrine disorders.

Gut microbiota composition is unique in every individual, it impacts on organ functions that produce hormones. Gut microbiota composition balance is directly related to our general health status. This continual interaction between gut microbiota and endocrine organs sometimes can be considered as the etiology of diseases such as type 2 diabetes mellitus (T2DM), obesity, osteoporosis, polycystic ovary syndrome (PCOS), and thyroid diseases. Microbiota is introduced for a total collection of microbial organisms in our bodies and microbiome referred for their genome and their collective functions. Near 100 trillion microorganisms live in our body and almost all of them occupy the human gut gastrointestinal tract. Precision medicine can play a crucial role in health maintenance by affecting gut microbiota composition in every individual. It can also develop special treatments specifically for every individual. In this review, we addressed any correlation between gut microbiota and endocrine disorders including T2DM, obesity, PCOS, thyroid disorders and osteoporosis.

A narrative review of current trends in liraglutide: insights into the unmet needs in management of type 2 diabetes and obesity.

Liraglutide is a long-acting human glucagon-like peptide-1 (GLP-1) analogue and an effective treatment for patients with metabolic diseases including type 2 diabetes mellitus (T2DM) and obesity. This review focuses on the mechanism of action of liraglutide as a well-known glucagon-like peptide-1 receptor agonist (GLP-1 RA) in patients with T2DM and obesity. The lower and the higher doses of GLP-1 RAs are used for glycaemic control in T2DM and in obesity respectively. GLP-1 RAs such as liraglutide enhance insulin secretion and inhibit glucagon release via the stimulation of glucagon-like peptide-1 receptors (GLP-1Rs). Liraglutide decreases hemoglobin A1c (HbA1c) in type 2 diabetes (T2D) patients when prescribes as monotherapy or in combination with one or more antidiabetic drugs. Usually, it is well tolerated with minor hypoglycemia in combination therapy. Liraglutide reduces cardiovascular events and related risk factors including improvement of lipid profile and control of blood pressure. Accordingly, it can be cost-effective and may be a budget neutral medication option by considering its protective effect on the cardiovascular system in long-term use in the health care plan. In the near future, by pharmacogenomics approach, prediction of the highest patient's response with the lowest adverse drug reactions and also rationality of drug development will be possible. Liraglutide can be used as a desirable medicine for glycemic control and obesity. It shows extensive evidence based benefits in diabetes complications. In this narrative review, we have summarized and evaluated studies related to the role of liraglutide in clinical practice.

Kallikarein-related peptidase 3 common genetic variant and the risk of prostate cancer.

Kallikarein-related peptidase 3 (KLK3) gene polymorphisms seem to play a role in susceptibility to prostate cancer (PC). The purpose of this study was to investigate the association between rs2735839 polymorphism of KLK3 gene and risk of PC in an Iranian population. In this case-control study, rs2735839 was genotyped in 532 patients with PC and 602 controls with benign prostate hyperplasia (BPH) using polymerase chain reaction-restriction fragment length polymorphism assay. The frequency of GG, AG, and AA genotypes of KLK3 polymorphism was 24.6% and 76.2%, 46.6% and 21.7%, and 28.8% and 2.1%, in patients with BPH and PC, respectively (P < 0.001). The frequency of G allele in patients with BPH and PC was 47.9% and 87%, respectively (odds ratio: 7.31; confidence interval: 5.88-9.10; P < 0.001). Patients with AG and GG genotypes had a higher total serum level of prostate-specific antigen (PSA) compared to those with AA genotype (P < 0.001). Patients with this polymorphism had higher risk of tumor with higher grade (P = 0.23), advanced stage (P = 0.11), perineural invasion (P = 0.07), and vascular invasion (P = 0.07) compared to those without it but this difference was not statistically significant. Based on our results, KLK3 gene polymorphism was associated with the risk of PC. Higher levels of PSA in the presence of KLK3 polymorphism in patients with PC indicated that rs2735839 polymorphism could be a risk factor for increased levels of PSA.

Association of vascular endothelial growth factor (VEGF) Gene polymorphisms and expression with the risk of endometriosis: a case-control study.

Endometriosis is a polygenic and multifactorial gynecology situation which might be associated with angiogenesis. In the current study we assess the role of vascular endothelial growth factor (VEGF) - 2578 A/C, and + 936 C/T polymorphisms in susceptibility to endometriosis and checking the expression of VEGF mRNA in eutopic tissue of endometrium with and without endometriosis. The study was comprised of 300 patients who underwent laparascopic or laparotomy surgery with 100 cases who had confirmed histological diagnosis of endometriosis, and 200 controls with no histological diagnosis of disease. The genotyping of VEGF polymorphisms was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique and the gene expression in tissue was determined using Real-Time PCR assay. There was no important difference of allele distribution of the - 2578 A/C (P = 0.7) and + 936 C/T (P = 0.5) polymorphisms among endometriosis cases and controls. Study of VEGF expression during the menstrual cycle, showed that endometrial tissue in cases group expressed more VEGF mRNA at the secretory phase compared to the proliferative phase (P = 0.03). Our results suggest that - 2578 A/C and + 936 C/T polymorphisms of VEGF did not seem to have impact on endometriosis predisposition in our study population. Also we did not find any link between VEGF mRNA expression and risk of endometriosis.