RAGE Gene Polymorphisms Research Articles

IDF23-0338 Association of RAGE gene polymorphism with Type 2 diabetes mellitus and renal function in the Mexican population

IDF23-0338 Association of RAGE gene polymorphism with Type 2 diabetes mellitus and renal function in the Mexican population

The Association of HMGB1 and RAGE Gene Polymorphisms with IgA Vasculitis.

High-mobility group box 1 (HMGB1) is a pleiotropic cytokine that propagates inflammation by its extracellular action of interacting with the receptor for advanced glycation end products (RAGE). Both HMGB1 and RAGE play multiple roles in the pathogenesis of a variety of inflammatory and autoimmune diseases. We investigated the association of five single-nucleotide polymorphisms (SNPs) of the HMGB1 gene (rs1412125, rs2249825, rs1045411, rs1060348, rs41369348) and four SNPs of the RAGE gene (rs1800624, rs1800625, rs2070600, rs3134940) with the susceptibility and clinical features of paediatric patients with IgA vasculitis (IgAV), also known as Henoch-Schönlein's purpura. This case‒control study included 103 children with IgAV (experimental group) and 150 age-matched healthy individuals (control group). The strength of the association between different groups and alleles or genotypes of HMGB1 and RAGE was estimated using odds ratios (ORs) and 95% confidence intervals (CIs). The HMGB1 polymorphisms rs41369348, rs1045411, rs2249825 and rs1412125 were associated with the development of generalized purpuric rash, and rs1412125 was associated with IgAV nephritis (IgAVN). The RAGE polymorphism rs2070600 might be linked to the development of arthritis in IgAV patients. There was no statistically significant association between the analysed polymorphisms and susceptibility to IgAV. This is the first study to propose an association between several HMGB1 and RAGE polymorphisms and different phenotypes in the clinical course of IgAV in a paediatric population. Further research on other polymorphisms of HMGB1 and RAGE should be conducted in a larger number of patients.

Nanopore Sequencing of RAGE Gene Polymorphisms and Their Association with Type 2 Diabetes.

The receptor for advanced glycation end products (RAGE) is a transmembrane protein that interacts with its ligands, advanced glycation end products (AGEs). AGEs are elevated in diabetes and diabetic complications, leading to increased oxidative stress and activation of pro-inflammatory pathways facilitated by AGE-RAGE signaling. Polymorphisms in the RAGE gene can potentially affect AGE-RAGE interaction and its downstream signaling, which plays a crucial role in the progression of diabetes and its complications. In this study, we used nanopore sequencing for genotyping of RAGE polymorphism and identified a maximum number of 33 polymorphisms, including two previously unreported novel mutations in a cohort of healthy, type 2 diabetics without nephropathy and type 2 diabetics with nephropathy in order to identify associations. Two novel RAGE polymorphisms in the intron 8 and 3'UTR region at genomic locations 32181834 and 32181132, respectively, were detected with a low frequency. For four previously reported polymorphisms, cross-validation by PCR-RFLP showed 99.75% concordance with nanopore sequencing. Analysis of genotype distribution and allele frequencies revealed that five single nucleotide polymorphisms, i.e., rs1800625, rs3131300, rs3134940, rs2070600, and rs9391855, were associated with an increased risk for type 2 diabetes.

Determination of the effects of advanced glycation end products receptor polymorphisms and its activation on structural cell responses and inflammation in asthma.

Advanced glycation end products receptor (RAGE) is a pattern recognition receptor which attracted attention in chronic airway diseases recently. This study aimed to determine the association of RAGE with asthma and the cellular responses resulting from RAGE signaling pathway activation. Asthmatic (n = 362) and healthy (n = 134) children were genotyped by PCR-RFLP. Plasma sRAGE levels were determined by ELISA. Lung structural cells were stimulated with AGEs (advanced glycation end products) and control BSA. Expressions of cytokines and protein levels were determined by real-time PCR and ELISA. : Gly82Ser and -374 T/A polymorphisms in RAGE gene were associated with lower plasma sRAGE levels (p < 0.001 and p < 0.025, respectively). AGE stimulation increased the expression of RAGE (p = 0.002), ICAM-1 (p = 0.010) and VCAM-1 (p = 0.002) in endothelial cells; TIMP-1 (p = 0.003) and MCP-1 (p = 0.005) in fibroblasts. AGE stimulation increased protein levels of IL-6 (p < 0.001) in endothelial cells; VEGF (p = 0.025) and IL-8 (p < 0.001) in fibroblasts; IL-1b (p < 0.001) and VEGF (p = 0.007) in epithelial cells. Activation of RAGE pathway may contribute to asthma pathogenesis by increasing the expression of several asthmarelated genes. These findings suggest that suppression of RAGE signaling may be an alternative candidate for treating asthma.

Evaluation of advanced protein oxidation and RAGE gene variants in the risk of laryngeal cancer

Laryngeal tumours with multifactorial etiopathogenesis constitute ∼1% of all body cancers. The imbalance between oxidative and antioxidative systems affects redox-homeostasis. The oxidative stress generated by the continuous formation of reactive oxygen species results in the oxidation of cellular molecules. The present study investigated the protein oxidation levels and the distribution of receptors for advanced glycation end products (RAGE) variants in the risk of laryngeal carcinoma (LC). RAGE gene polymorphisms were determined by restriction endonuclease-based assay in 120 controls and 120 LC patients. Spectrophotometric methods were used to determine oxidant and antioxidant parameters including protein-carbonyl-groups (PCO), advanced-oxidation-protein-products (AOPP), lipid-hydroperoxides (LPH), thiol-fractures, superoxide-dismutase (SOD) activity. The distributions of rs1800624 and rs2070600 genotypes differed non-significantly among the study groups, however, the rs2070600-Ser allele had a higher frequency among the patients. While rs1800624-A allele carriers had higher frequency of perineural and lymphatic invasion, rs2070600-Ser allele frequency was higher in advanced-stage patients and in patients with muscle and perineural invasion. PCO, AOPP, LPH levels, and SOD activity were significantly higher in the patients. According to AUCs all of them are of diagnostic importance, therefore, cut-off values were determined. The analysis of the combined effects of RAGE polymorphisms and the oxidative stress parameters showed that LPH, thiols, and SOD activity differ among RAGE variants. Our results suggest that high levels of serum PCO, AOPP, LPH, and SOD activity and rs2070600-Ser allele may have effects on LC risk individually and both polymorphisms of RAGE may affect the progression of the disease by interacting with the oxidant–antioxidant system.

Study of Association between RAGE Gene Polymorphism rs2070600 (G82S) and Aspirin Resistance in Coronary Artery Disease Iraqi Patients with and without Type 2 Diabetes

Study of Association between RAGE Gene Polymorphism rs2070600 (G82S) and Aspirin Resistance in Coronary Artery Disease Iraqi Patients with and without Type 2 Diabetes

Role of rs 1800625 and 63bp deletion RAGE Gene Polymorphisms in Hepatocellular Carcinoma Progression

Background: Hepatocellular carcinoma (HCC) is a common liver malignancy, whose heterogeneous occurrence indicates genetic dissimilarities between people in the main risk factors. Advanced glycation end product receptor (RAGE) is a multiligand receptor implicated in several pathogenic conditions, including cancer. In this study, the impact of RAGE gene polymorphisms on the susceptibility to hepatocarcinogenesis was explored. Aim of study: to estimate the effect of gene variations of RAGE on the progress of HCC caused by any viral infection and to examine the relationship between a RAGE and the risk and progression of HCC. Material and methods: single-nucleotide polymorphism (SNP; rs1800625) (-429T>C), and the 63 bp deletion (-407 to -345) in the 5’ flanking region of the RAGE gene were investigated among 90 HCV patients divided into 3 groups and 20 healthy controls. The HCV cases were diagnosed by polymerase chain reaction (PCR) while the HCC was diagnosed by Alfa-fetoprotein (AFP) test in addition to computed tomography. Liver cirrhosis was diagnosed with abdominal sonography. Results and conclusion: The study detected a significant association of rs1800625 with the increased risk of HCC also majority of HCC patient (86.7%) showed 63 bp deletion polymorphism (- 407 – 345 ) , our data suggest a correlation of RAGE gene polymorphism rs1800625 with the early stage of liver tumorigenesis and implicate its protective role in the progression of HCC.

Association of RAGE gene polymorphisms with MHR ratio and heart rate variability among patients with coronary heart disease

To assess the association of polymorphisms of receptor of advanced glycation end products (RAGE) gene, monocyte to high-density lipoprotein cholesterol ratio (MHR) and variability of heart rate among patients with coronary heart disease (CHD). 120 patients with CHD and 120 healthy individuals were respectively selected as the observation group and the control group. Allelic and genotypic differences of -429T>C, 1704G>T, 82G>S, MHR ratio and heart rate variability between the two groups and patients with different severity were analyzed. The correlation between their genotypes and MHR ratio and heart rate variability was analyzed. The 82G>S polymorphism of the RAGE gene and the allelic difference between the two groups and patients with different severity were statistically significant (P< 0.05). Compared with the control group and patients with mild to moderate phenotype, monocyte, total cholesterol, triglyceride, low density lipoprotein, MHR, low frequency in the observation group and patients with severe symptoms were significantly higher, while their high density lipoprotein, standard deviation of NN intervals (SDNN), standard deviation average of NN intervals (SDANN), root mean square successive differences, percentage of differences exceeding 50ms between adjacent normal number of intervals (PMN50), high frequency (HF) were significantly lower. The gene frequencies of G-Gly-T, T-Gly-T, G-Ser-T and G-Gly-C were correlated with SDNN, SDANN, rMSSD, PMN50, HF and MHR, but negatively correlated with low frequency. Polymorphisms of the RAGE gene in patients with coronary heart disease are associated with the MHR ratio and heart rate variability, which can be used as markers for the diagnosis and efficacy evaluation.

Hyperactivated RAGE in Comorbidities as a Risk Factor for Severe COVID-19-The Role of RAGE-RAS Crosstalk.

The receptor for advanced glycation-end products (RAGE) is a multiligand receptor with a role in inflammatory and pulmonary pathologies. Hyperactivation of RAGE by its ligands has been reported to sustain inflammation and oxidative stress in common comorbidities of severe COVID-19. RAGE is essential to the deleterious effects of the renin–angiotensin system (RAS), which participates in infection and multiorgan injury in COVID-19 patients. Thus, RAGE might be a major player in severe COVID-19, and appears to be a useful therapeutic molecular target in infections by SARS-CoV-2. The role of RAGE gene polymorphisms in predisposing patients to severe COVID-19 is discussed.

Polymorphisms of the receptor for advanced glycation end products as vasculopathy predictor in sickle cell disease.

The genetic variants of the receptor for advanced glycation end products (RAGE) gene have been associated with vascular disease risk. The objective of this work was to explore the association of three single-nucleotide polymorphisms (SNPs) of RAGE gene (374T/A, 429T/C, and G82S) with vascular complications in SCD. The study was conducted on 40 children with SCD and 40 healthy children served as controls. All participants were genotyped for the three studied RAGE polymorphisms by polymerase chain reaction (PCR). Regarding 374T/A polymorphism, the frequency of TA, TT genotypes and T allele were higher in patients (p < 0.001). T allele was associated with higher incidence of sickling crisis and stroke (p < 0.05). In the subgroup analyses of 429T/C polymorphism, an association between C allele and SCD vascular complications was observed (p < 0.05). Concerning the frequency of G82S genotypes of RAGE, GG variant was detected in 39 (97.5%) of the patients, as compared with 40 (100%) of controls (p = 0.3). A regression analysis proved that HbS%, serum ferritin, and the -374T and 429C alleles were significant independent predictors of frequent sickling episodes (p < 0.05). The C allele of -429T/C and T allele of 374T/A RAGE polymorphisms may be considered as predictors for vascular dysfunction in SCD. The C allele of -429T/C and T allele of 374T/A RAGE polymorphisms may be considered as predictors for vascular dysfunction in SCD patients. To our knowledge, our study is the first exploring the association of three single-nucleotide polymorphisms of RAGE gene (374T/A, 429T/C, and G82S) with vascular complications in SCD. Early identification of patients carrying these genetic variants might be of great importance not only to identify subjects at risk of vasculopathy but also to direct them to RAGE-targeted treatments.

SUN-LB131 Association of Receptor for Advanced Glycation End Product (RAGE) Gene Polymorphisms &amp; Serum Levels of Soluble RAGE (sRAGE) With Metabolic Syndrome (MS) in Mexican Population

Background. RAGE, a multi-ligand type 1 transmembrane glycoprotein belonging to the immunoglobulin superfamily, transduces biological signals associated with chronic cellular stress related with inflammatory responses, tissue damage, chronic and degenerative diseases (1). sRAGE is a variant of RAGE derived from cell surface cleavage mechanisms that could potentially act as endogenous inhibitors of RAGE activity (2). RAGE gene is highly polymorphic, with polymorphisms that could be responsible for disease development, like -374T/A (rs1800624) and -429T/C (rs1800625) polymorphisms. These are located in the promoter region and have marked effect on transcriptional activity. However, there have been conflicting findings between the potential association of RAGE polymorphisms and the development of diseases. In this work, we evaluated -374T/A (rs1800624) and -429T/C (rs1800625) polymorphisms and measured serum sRAGE levels in Mexican population with MS. Methods. A group of healthy men without any component of the MS (n=80), and a group of men with the MS (n=80) according to the harmonized criteria for the MS were included in this study. Blood genomic DNA was isolated and genotyped by RT-PCR for the -374T/A and -429T/C polymorphisms of RAGE gene. sRAGE in serum was measured with an ELISA kit. Results. The studied population complied with the Hardy-Weinberg equilibrium (p=0.58 for -374T/A, and p=0.79 for -429T/C). Differences were observed in all the components of the MS between the two groups (MS vs. healthy subjects, p<0.000). However, there were no differences in the population according to their genotype for the -374T/A (p=0.57) and -429T/C (p=0.59) polymorphisms. There was no difference in glucose (p=0.22), triglycerides (p=0.99), and cHDL (p=0.88) levels, or waist circumference (p=0.84) according to the genotype for the -374T/A polymorphism. The same was observed for the -429T/C polymorphism (glucose p=0.57, triglycerides p=0.69, cHDL p=0.77, waist circumference p=0.99). No association of MS with the -374T/A nor 429T/C polymorphism was found. There were no differences between groups in circulating sRAGE levels (p=0.132). Conclusion. According to our results, the -374T/A and -429T/C polymorphisms of RAGE gene are not associated with the MS in Mexican population, and have no influence on serum sRAGE levels. Some other factors could be playing a role for the high prevalence of the MS, such as eating habits. Gender should be taken into consideration, for our study was performed in men exclusively. References. (1) Serveaux-Dancer M et al., Dis Markers. 2019 Feb 4;2019:2067353. (2) Schmidt AM. Vascul Pharmacol. 2015 Sep;72:1-8.

Receptor for advanced glycation end products gene polymorphisms in cardiac syndrome X.

Endothelial and microvascular dysfunction serve important roles in the formation and pathogenesis of cardiac syndrome X (CSX). Expression of receptor for advanced glycation end products (RAGE) is suggested to be increased in several conditions, including diabetes, inflammation and vascular diseases. In the present study, RAGE gene polymorphisms in patients with CSX and healthy controls were investigated. A total of 114 patients, diagnosed with CSX using coronary angiography results following complaints of angina and objective ischemia, and 103 healthy controls participated in the study. Whether there was a difference in genotype distributions of RAGE gene -374T/A, -429T/C and Glys82Ser polymorphisms between patients with CSX and healthy controls was investigated. Following DNA isolation from blood samples of the participants, the polymorphic regions were examined by quantitative polymerase chain reaction, and the genotyping results were statistically analyzed. When the genotypic distributions of -374T/A, -429T/C and Gly82Ser polymorphisms were investigated in patients with CSX and healthy controls, no statistically significant differences were identified between the two groups (P>0.05). Likewise, no statistically significant differences were observed in the allelic distributions of all 3 polymorphic regions (P>0.05). To the best of our knowledge, the present study also investigated the association between CSX and RAGE gene polymorphisms for the first time. No statistically significant differences in RAGE gene polymorphisms between the CSX and control groups were observed. We hypothesized that significant results may be obtained by increasing the numbers of patients and healthy controls in future studies.

1081 - Impact of RAGE gene polymorphisms on urothelial cell carcinoma clinicopathologic characteristics and long term survival

1081 - Impact of RAGE gene polymorphisms on urothelial cell carcinoma clinicopathologic characteristics and long term survival

Relationship between RAGE gene polymorphisms and cardiovascular disease prognosis in the Chinese Han population.

Cardiovascular disease (CVD) is the leading cause of death in China. This study aimed to investigate whether RAGE gene polymorphisms are associated with the prognosis of various cardiovascular diseases in the Chinese Han population. This study was conducted from July 2004 to December 2005 and a total of 425 subjects from Guangdong province were enrolled. Genotyping of the three polymorphisms (-429T/C, 1704G/T, and G82S) in the RAGE gene was performed with polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP). Patients were followed for 6.5years to watch for the development of cardiovascular events and mortality. Subjects with the S mutation of the G82S polymorphism had a significantly higher risk of all-cause mortality and acute myocardial infarction (AMI) than did those with wild-type homozygosity. Logistic regression analysis and Kaplan-Meier analysis all revealed that the G82S polymorphism of the RAGE gene was associated with a significantly increased risk of all-cause mortality and AMI. However, the -429T/C and 1704G/T polymorphisms were not shown to have any effect on prognosis. In conclusion, the G82S variant of the RAGE gene was significantly associated with an increased risk of all-cause mortality and AMI in the Chinese Han population.

Effect of RAGE gene polymorphisms and circulating sRAGE levels on susceptibility to gastric cancer: a case\u2013control study

BackgroundTo investigate the influence of polymorphisms in the receptor for advanced glycation end products (RAGE) gene and circulating soluble RAGE (sRAGE) levels on susceptibility to gastric cancer, and identify whether these polymorphisms were correlated with serum sRAGE levels.MethodsWe performed a hospital-based case–control study involving 200 gastric cancer patients and 207 cancer-free controls. Four well-characterized RAGE genetic polymorphisms, namely, rs1800624, rs1800625, rs184003, and rs2070600 were genotyped by PCR–RFLP.ResultsThe rs2070600 AG genotype might play a predominant role in the development of gastric cancer (adjusted OR 1.62, 95% CI 1.03–2.58). In contrast, the rs184003 GT genotype represented significantly reduced risk for gastric cancer (adjusted OR 0.62, 95% CI 0.39–0.99). Subgroup analysis demonstrated that rs2070600 AG variant genotype enhanced the gastric cancer risk among nonsmokers (OR 1.71, 95% CI 1.01–2.91), nondrinkers (OR 1.75, 95% CI 1.03–2.97), and patients with tumor stage III (OR 2.00, 95% CI 1.13–3.56). The average sRAGE levels in the gastric cancer patients were significantly decreased compared with those of the healthy controls. Subjects carrying the rs2070600 AG genotype had a decreased ability to produce sRAGE. Subjects carrying the rs184003 T variant allele had an increased ability to sRAGE.ConclusionsThese findings suggested that the variant genotypes of rs184003 and rs2070600 in the RAGE gene exhibit significant associations with gastric cancer risk and circulating sRAGE levels inverse change simultaneously, leading to a marked causal estimate between lowered sRAGE levels and increased gastric cancer risk.

Evaluation of functional RAGE gene polymorphisms in childhood acute lymphoblastic leukemia—A case-control study from Iran

ABSTRACTWe examined the possible relationship between three RAGE polymorphisms, −429C/T, −374 T/A, and 63-bp deletion, and susceptibility to childhood acute lymphoblastic leukemia (ALL) in an Iranian population. This study included 75 ALL patients and 115 healthy subjects. Genotyping was performed using HEXA-ARMS-polymerase chain reaction. We found no significant association among RAGE gene polymorphisms and the risk for ALL at genotype, allelic and haplotype levels (P > 0.05). The hemoglobin levels were higher in patients with RAGE −374 TT than in the TA carriers (P = 0.019). Our results demonstrated that the RAGE gene variations were not associated with risk of pediatrics ALL.

Genetic association between RAGE polymorphisms and Alzheimer's disease and Lewy body dementias in a Japanese cohort: a case-control study.

Interaction of receptor for advanced glycation end products (RAGE) with amyloid-β increases amplification of oxidative stress and plays pathological roles in Alzheimer's disease (AD). Oxidative stress leads to α-synuclein aggregation and is also a major contributing factor in the pathogenesis of Lewy body dementias (LBDs). Therefore, we aimed to investigate whether RAGE gene polymorphisms were associated with AD and LBDs. Four single nucleotide polymorphisms (SNPs)-rs1800624, rs1800625, rs184003, and rs2070600-of the gene were analyzed using a case-control study design comprising 288 AD patients, 76 LBDs patients, and 105 age-matched controls. Linkage disequilibrium (LD) examination showed strong LD from rs1800624 to rs2070600 on the gene (1.1 kb) in our cases in Japan. Rs184003 was associated with an increased risk of AD. Although there were no statistical associations for the other three SNPs, haplotypic analyses detected genetic associations between AD and the RAGE gene. Although relatively few cases were studied, results from the SNPs showed that they did not modify the risk of developing LBDs in the Japanese population. Our findings suggested that polymorphisms in the RAGE gene are involved in genetic susceptibility to AD. Copyright © 2016 John Wiley & Sons, Ltd.

The promoter polymorphisms of receptor for advanced glycation end products were associated with the susceptibility and progression of sepsis.

Receptor for advanced glycation end products (RAGE) is considered a major pattern recognition receptor, which plays an important role in the development of sepsis. Increasing evidence showed an association between RAGE polymorphisms and the susceptibility to several inflammatory-related diseases. However, little is known about the clinical relationship between RAGE polymorphisms and sepsis. In this study, we analyzed the association of sepsis with three functional RAGE gene polymorphisms (rs1800624, rs1800625 and rs2070600) in a Chinese Han population (372 sepsis cases and 400 healthy controls). Significant differences were observed in the rs1800624 and rs1800625 genotype/allele distributions between the sepsis and controls, but no significant difference was observed in the rs2070600 genotype/allele. Moreover, our results also revealed a significant difference in the genotype/allele frequencies of the rs1800624 and rs1800625 polymorphisms between the sepsis and severe sepsis subtypes, the rs1800624 TT or rs1800625 TT genotype carriers exhibited a significant increase in RAGE mRNA, sRAGE, TNF-α and IL-6 expression compared with the rs1800624 AT/AA or rs1800625 CT/CC carriers in sepsis patients. Overall, this study might provide valuable clinical evidence between the RAGE gene polymorphisms and the risk or the development of sepsis.

Soluble receptor and gene polymorphism for AGE: relationship with obesity and cardiovascular risks.

Obesity in adolescents has quadrupled in the past 30 y. Markers for cardiovascular risks are needed in this population. We hypothesized that soluble receptor for advanced glycation end products (sRAGE) and asymmetric dimethyl arginine (ADMA) can correlate with carotid intima-media thickness (cIMT), a known index of subclinical atherosclerosis. We also aimed to evaluate the frequency of (Gly82Ser) RAGE gene polymorphism in obese adolescents. Obese and nonobese adolescents were evaluated in a cross-sectional study for lipid profile, insulin resistance, ADMA, sRAGE, and RAGE gene (Gly 82 Ser) polymorphism. We measured cIMT in all subjects and performed correlation analyses with all markers. The study included 50 obese and 40 healthy control adolescents. Compared to controls, obese subjects had less sRAGE (P = 0.02) and greater cIMT (P = 0.006), insulin resistance (P < 0.0001), and ADMA (P < 0.0001). In a multivariate linear regression model, sRAGE was associated with cIMT (β = 0.28, P = 0.04). Both GS and SS genotypes of RAGE were more frequent in obese than controls (P = 0.04). Increased ADMA and decreased sRAGE are associated with cardiovascular risks in obese adolescents. The S allele in RAGE gene is more frequently detected with obesity. The role of RAGE gene and mechanisms leading to cardiovascular risks need further studying.

The Association of -429T>C and -374T>A Polymorphisms in the RAGE Gene with Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a complex disorder characterized by hyperandrogenism and insulin resistance. In addition, a number of females with PCOS have ovaries with multiple cysts, an irregular or no menstrual cycle, and an imbalance of female hormones compared to those of normal controls. A variety of genetic factors have been involved in the pathogenesis of PCOS. Among these genetic factors, the receptor for advanced glycation end products (RAGE) that is associated with diabetes and involved in the complications of PCOS, was selected. We aimed to assess the relationship between -429T>C and -374T>A single nucleotide polymorphisms (SNPs) of RAGE gene with the susceptibility to PCOS.128 controls and 265 PCOS patients were used for -374T>A polymorphism and 141 controls and 290 PCOS patients were used for -429T>C polymorphism, respectively. Genotyping of two polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay and statistical analysis was performed. P values for both alleles were higher than 0.05. Frequencies of genotype and allele of two polymorphisms in RAGE gene showed no significant differences between controls and PCOS patients. The initial study on the correlation between RAGE gene and PCOS indicates that the two polymorphisms of RAGE are not associated with the pathogenesis of PCOS. However, further studies regarding the association between RAGE gene and PCOS patients in different ethnic groups are required.