Resistin Research Articles

Analysis of the relationship between resistin with prognosis, cell migration, and p38 and ERK1/2 activation in breast cancer

Obesity increases the risk and mortality of breast cancer through dysregulated secretion of proinflammatory cytokines and tumor adipokines that induce an inflammatory breast microenvironment. Resistin is an adipokine secreted by adipocytes, immune cells, and predominantly macrophages, which contributes to cancer progression, but its molecular mechanism in cancer is not completely described. In this study, we analyzed the relationship of resistin on breast cancer prognosis and tumor progression and the effect in vitro of resistin on p38 and ERK1/2 activation in breast cancer cell lines. By bioinformatic analysis, we found that resistin is overexpressed in the basal subtype triple-negative breast cancer and is related to poor prognosis. In addition, we demonstrated a positive correlation between RETN and MAPK3 expression in basal triple-negative breast cancer. Importantly, we found amplifications of the RETN gene in at least 20 % of metastatic samples from patients with breast cancer. Most samples with RETN amplifications metastasized to bone and showed high expression of IL-8 (CXCL8) and IL-6 (IL6). Finally, resistin could be considered a prognostic marker for basal triple-negative breast cancer, and we also proposed the possibility that resistin-induced cell migration involves the activation of MAPK in breast cancer cells.

Clinical significance of RETN gene expression and rs3219175 G > a polymorphism in cancer

The inflammatory cytokine resistin, which is encoded by the RETN gene, plays a variety of roles in cancer. This study aimed to assess the relationship between RETN gene expression and cancer stage, survival prognosis, immune infiltration, and drug sensitivity, and whether the rs3219175 G > A polymorphism affected the expression of the RETN gene and cancer risk. The clinical significance of RETN gene expression and the rs3219175 polymorphism in cancer was analyzed by the GSCA platform, GTEx database and STATA software. The results showed that RETN gene expression was associated with the stage of thyroid carcinoma, survival prognosis and immune infiltration of certain cancers, and sensitivity to multiple drugs. The rs3219175 polymorphism could influence the expression of the RETN gene in a wide range of tissues. Furthermore, RETN gene rs3219175 polymorphism was significantly associated with cancer risk [GA vs. GG: OR = 2.27, 95%CI = 1.26–4.09; (GA + AA) vs. GG: OR = 2.23, 95%CI = 1.28–3.88; A vs. G: OR = 1.72, 95%CI = 1.15–2.58]. In conclusion, the current study suggested that resistin might serve as a prognostic marker and therapeutic target for certain cancers, and the rs3219175 polymorphism might be used as a marker for predicting cancer risk.

The Gene Network Correlation Analysis of Obesity to Type 1 Diabetes and Cardiovascular Disorders: An Interactome-Based Bioinformatics Approach.

The current study focuses on the importance of Protein-Protein Interactions (PPIs) in biological processes and the potential of targeting PPIs as a new treatment strategy for diseases. Specifically, the study explores the cross-links of PPIs network associated with obesity, type 1 diabetes mellitus (T1DM), and cardiac disease (CD), which is an unexplored area of research. The research aimed to understand the role of highly connected proteins in the network and their potential as drug targets. The methodology for this research involves retrieving genes from the NCBI online gene database, intersecting genes among three diseases (type 1 diabetes, obesity, and cardiovascular) using Interactivenn, determining suitable drug molecules using NetworkAnalyst, and performing various bioinformatics analyses such as Generic Protein-Protein Interactions, topological properties analysis, function enrichment analysis in terms of GO, and Kyoto Encyclopedia of Genes and Genomes (KEGG), gene co-expression network, and protein drug as well as protein chemical interaction network. The study focuses on human subjects. The results of this study identified 12 genes [VEGFA (Vascular Endothelial Growth Factor A), IL6 (Interleukin 6), MTHFR (Methylenetetrahydrofolate reductase), NPPB (Natriuretic Peptide B), RAC1 (Rac Family Small GTPase 1), LMNA (Lamin A/C), UGT1A1 (UDP-glucuronosyltransferase family 1 membrane A1), RETN (Resistin), GCG (Glucagon), NPPA (Natriuretic Peptide A), RYR2 (Ryanodine receptor 2), and PRKAG2 (Protein Kinase AMP-Activated Non-Catalytic Subunit Gamma 2)] that were shared across the three diseases and could be used as key proteins for protein-drug/chemical interaction. Additionally, the study provides an in-depth understanding of the complex molecular and biological relationships between the three diseases and the cellular mechanisms that lead to their development. Potentially significant implications for the therapy and management of various disorders are highlighted by the findings of this study by improving treatment efficacy, simplifying treatment regimens, cost-effectiveness, better understanding of the underlying mechanism of these diseases, early diagnosis, and introducing personalized medicine. In conclusion, the current study provides new insights into the cross-links of PPIs network associated with obesity, T1DM, and CD, and highlights the potential of targeting PPIs as a new treatment strategy for these prevalent diseases.

Serum Resistin Levels in Patients with Nonalcoholic Fatty Liver Disease in an Iranian Population

Introduction: Non-alcoholic fatty liver disease (NAFLD) is a major global health problem, in which liver fat exceeds 5% of the liver weight, without secondary causes of fat accumulation or excessive alcohol consumption. Resistin plays a key role in energy homeostasis, insulin resistance, inflammation, and metabolic disorders. This study aimed to investigate the relationship between resistin (RETN) level and NAFLD. Methods: In this cross-sectional study, 80 patients with NAFLD and 80 healthy individuals as controls were evaluated. Biochemical variables, liver enzymes, insulin, and resistin were measured. Data were analyzed using SPSS version 16 software. Results: The variables of cholesterol, insulin, triglyceride, HDL, body mass index, age, and liver enzymes were significantly different between the two groups of patients with NAFLD and healthy individuals (p<0.05). In patients, resistin was associated with triglyceride (r=0.243, p=0.045). No association was found between resistin level and NAFLD grades (p≥0.05). Conclusion: The results of this study indicate that there is a relationship between resistin and NAFLD. There is no association between resistin level and the degree of NAFLD.

Multiplex cytokine analysis for the identification of novel potential synovial fluid biomarkers for periprosthetic joint infections

IntroductionPeriprosthetic joint infections (PJIs) are a devastating complication of total hip (THA) and knee (TKA) arthroplasty. The use of novel techniques like multiplex cytokine analysis could contribute immensely to the identification of potential novel biomarkers. Patients and MethodsThis is a single-centre study of patients that were treated with revision TKA, THA or hemiarthroplasty. Serum's white blood cells (WBCs), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) and synovial fluid's WBCs, percentage of polymorphonuclear neutrophils (%PMNs) and CRP were measured. Proteomic analysis targeting the secreted cytokines in synovial fluid was conducted using a 73-plex assay panel. The results were statistically compared between the septic and aseptic cases and ROC analysis to establish the area under the curve (AUC), sensitivity and specificity of each biomarker. ResultsThe study included 30 patients (18 revision THA cases; 3 conversion of hemiarthroplasty to THA and 9 revision TKA cases); 14 cases were considered infected, 1 likely infected and 15 not infected. The results showed statistically significant differences (p < 0.05) between infected and not infected cases in serum's ESR, CRP and synovial fluid's%PMNs, growth-regulated oncogene alpha (GROA), interleukin-8, interleukin-5, S100-A8/calprotectin and resistin (RETN) with AUCs of 0.75, 0.72, 0.95, 0.75, 0.72, 0.95, 0.83, 0.73, 0.75, 0.81 and 0.76 respectively. ConclusionsIn the present study, serum ESR and CRP as well as synovial %PMNs, GROA, IL-8, IL-5, calprotectin and RETN protein levels were identified as potential biomarkers. Further studies are needed to further investigate their diagnostic utility and optimal cut-off values.

Abstract PO5-05-08: LOSS OF SINGLEMINDED 2S RESULTS IN A PI3K SUBUNIT SWITCH WHICH DRIVES THERAPEUTIC RESISTANCE IN ESTROGEN RECEPTOR POSITIVE BREAST CANCER

Abstract Estrogen receptor (ER) + breast cancer (BC) comprises over 70% of BC cases and are targeted via ER modulated therapies. Despite this, ER+BC patients can experience recurrence within 20 years and the majority of BC related deaths can be attributed to metastatic ER+BC. These distant metastases are commonly diagnosed as endocrine therapy resistant. Thus, there is an unmet need to identify novel biomarkers for treating ER+ patients with metastases. We have identified a tumor suppressor gene, singleminded 2s (SIM2s), expressed in breast epithelial cells that inhibits epithelial to mesenchymal transition and metastasis, and is downregulated in the progression of breast disease. In ER+BC cell lines, loss of SIM2s results in upregulation of mesenchymal markers and increased PI3K/Akt signaling. Dysregulation of the PI3K/Akt signaling pathway in ER+BC is involved with tumor progression and acquired therapeutic resistance. Our study suggests loss of SIM2s confers resistance in ER+BC through a PI3K subunit switch resulting in upregulation of pro-survival signaling. MCF7 SIM2 knock out cells exhibit increased expression of mesenchymal markers and undergo a phenotypic change compared to wild type cells. Utilizing a migration/invasion assay, MCF7 SIM2 knock out cells exemplify an increase in invasion potential compared to wild type cells. Furthermore, changes in PI3K subunit expression were observed via western blot and real time qPCR analysis. Clonogenic assays revealed an acquired resistance to PI3Kα inhibition, but a susceptibility to PI3Kδ inhibition. This is a significant finding as a current standard of care for patients with ER+ breast cancer recurrence is PI3Kα inhibition. PI3Kδ is an already approved therapeutic target in chronic lymphocytic leukemia, thus PI3Kδ may present a new therapeutically targetable opportunity for ER+BC recurrence. Elucidating the mechanism for acquired therapeutic resistance is an integral avenue for understanding how breast cancer progresses and improving the prognosis of ER+BC patients. Citation Format: Garhett Wyatt, Rachel Steinmetz, Traci Lyons, Weston Porter. LOSS OF SINGLEMINDED 2S RESULTS IN A PI3K SUBUNIT SWITCH WHICH DRIVES THERAPEUTIC RESISTANCE IN ESTROGEN RECEPTOR POSITIVE BREAST CANCER [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-05-08.

Nucleotide-binding leucine-rich repeat receptor homologs Pib and PibH8 interact and contribute to immunity in rice.

Plant nucleotide-binding leucine-rich repeat receptors (NLRs) sense pathogen effectors and activate effector-triggered immunity (ETI). Many plant NLRs form pairs with other NLRs to recognize effectors and initiate ETI. PIRICULARIA ORYZAE RESISTANCE IN BL1 (Pib), an NLR protein in rice (Oryza sativa), activates resistance by recognizing the rice blast effector AvrPib. The activation of Pib is suppressed by SH3 DOMAIN-CONTAINING PROTEIN 2 (OsSH3P2) in the absence of AvrPib. However, how Pib triggers defense responses and whether Pib pairs with another NLR are not clear. In this study, we identified Pib by map-based cloning and showed that a homolog of Pib, PIB HOMOLOGUE 8 (PibH8), interacts with Pib. Pib and PibH8 mediate resistance to the Magnaporthe oryzae isolate Guy11, a rice blast strain carrying AvrPib. Interestingly, the pib/pibh8 double mutant exhibited enhanced susceptibility to Guy11 compared to the single mutant. Furthermore, PibH8 can oligomerize through its coiled-coil (CC) domain, which also contributes to the Pib-PibH8 interaction, suggesting that Pib and PibH8 may form a complex to recognize AvrPib. OsSH3P2 inhibited the interaction of Pib and PibH8 through association with the CC domain of PibH8. Taken together, these results indicate that both Pib and PibH8 are required for rice blast resistance to M. oryzae carrying AvrPib, which is negatively regulated by OsSH3P2. This study not only identifies an NLR that functions in rice blast resistance but also reveals a possible complex immune strategy in which homologous NLR proteins may regulate the complete activation of plant immunity.

ULTRASONIC-ASSISTED ELECTRODEPOSITION OF CoMo/Al2O3 COMPOSITE COATING ON THE SURFACE OF STEEL AND ITS CORROSION RESISTANCE IN SIMULATED SEWAGE WATER

The ultrasonic is applied during the electrodeposition process of CoMo/Al2O3 composite coating on 10# steel to enhance its corrosion resistance in simulated sewage water. The influence of ultrasonic power on the thickness, roughness, chemical composition, surface morphology, and corrosion resistance of the composite coating is investigated. In an aqueous solution, a co-deposition of cobalt and molybdenum can be induced to form CoMo alloy coating. The Al2O3 nanoparticles are incorporated into CoMo alloy to form CoMo/Al2O3 composite coating. When the ultrasonic power increases from 0[Formula: see text]W to 100 W, the electrodeposition rate of the composite coating increases from 63.25[Formula: see text]mg/h to 153.73[Formula: see text]mg/h, and the thickness of the composite coating also increases from 15.6[Formula: see text][Formula: see text]m to 28.1[Formula: see text][Formula: see text]m. The surface roughness of composite coating electrodeposited without ultrasonic is about 0.436[Formula: see text][Formula: see text]m. The CoMo/Al2O3 composite coating electrodeposited at 100[Formula: see text]W ultrasonic power exhibits the smallest surface roughness of 0.193[Formula: see text][Formula: see text]m and presents a denser surface morphology composed of 74.4% Co, 10.3% Mo, and 15.3% Al, resulting in better corrosion resistance with the smallest corrosion current density of only 9.7[Formula: see text][Formula: see text]A/cm2. However, when the ultrasonic power is 150[Formula: see text]W, the intense hydrogen evolution on the surface of the cathode reduces the density of the coating surface, which leads to the deterioration of corrosion resistance.

Dysregulation of iron transport-related biomarkers in blood leukocytes is associated with poor prognosis of early trauma

ObjectiveThe early targeted and effective diagnosis and treatment of severe trauma are crucial for patients' outcomes. Blood leukocytes act as significant effectors during the initial inflammation and activation of innate immunity in trauma. This study aims to identify hub genes related to patients' prognosis in blood leukocytes at the early stages of trauma. MethodsThe expression profiles of Gene Expression Omnibus (GEO) Series (GSE) 36809 and GSE11375 were downloaded from the GEO database. R software, GraphPad Prism 9.3.1 software, STRING database, and Cytoscape software were used to process the data and identify hub genes in blood leukocytes of early trauma. ResultsGene Ontology (GO) analysis showed that the differentially expressed genes (DEGs) of blood leukocytes at the early stages of trauma (0–4 h, 4–8 h, and 8–12 h) were mainly involved in neutrophil activation and neutrophil degranulation, neutrophil activation involved in immune response, neutrophil mediated immunity, lymphocyte differentiation, and cell killing. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the DEGs were mainly involved in Osteoclast differentiation and Hematopoietic cell lineage. Sixty-six down-regulated DEGs and 148 up-regulated DEGs were identified and 37 hub genes were confirmed by Molecular Complex Detection (MCODE) of Cytoscape. Among the hub genes, Lipocalin 2 (LCN2), Lactotransferrin (LTF), Olfactomedin 4 (OLFM4), Resistin (RETN), and Transcobalamin 1 (TCN1) were related to prognosis and connected with iron transport closely. LCN2 and LTF were involved in iron transport and had a moderate predictive value for the poor prognosis of trauma patients, and the AUC of LCN2 and LTF was 0.7777 and 0.7843, respectively. ConclusionAs iron transport-related hub genes in blood leukocytes, LCN2 and LTF can be used for prognostic prediction of early trauma.

RESISTIN GENE POLYMORPHISMS: POTENTIAL BIOMARKER FOR ORAL SQUAMOUS CELL CARCINOMA

Objective: The objective of the work is to study the association between Resistin Gene polymorphisms and susceptibility of Oral Squamous Cell carcinoma. Methods: In the present study, we scrutinize the connection between four genetic polymorphisms present in RETN gene with the susceptibility, progression, and clinical outcome of OSCC among 200 OSCC patients and 200 healthy controls. Results: The results of the study reveal that among 260 smokers, the risk of developing OSCC is significantly more among the subjects having history of using betel quid in comparison to those who are not habitual users of betel quid. Conclusion: The study reveals that patients with OSCC exhibiting G/A heterozygous genotype of RETN rs3219175 polymorphism have lesser risk for developing high-grade tumor compared to the patients with G/G homozygotes in North Indian population.

Resistin in endocrine pancreas of sheep: Presence and expression related to different diets

Resistin (RETN), a recently discovered adipokine, is a cysteine-rich and secretory protein produced by adipocytes. RETN has been detected in several tissues, including human and laboratory animals' pancreas, wherein impairs glucose tolerance and insulin (INS) action and causes INS resistance. This study aims to evaluate the presence and expression of RETN in the pancreas of 15 adult female sheep reared on Apennine pastures, which show a decrease in their nutritional value due to the drought stress linked to the increasing summer aridity. The sheep were divided into 3 groups according to the diet they were subjected to: maximum pasture flowering (MxF) group, maximum pasture dryness (MxD) group, and experimental (Exp) group which received a feed supplementation in addition to the MxD group feeding. Immunohistochemistry and immunofluorescence were performed on formalin-fixed and paraffin-embedded sections of the pancreas to detect the RETN presence and to evaluate the co-localization of RETN with both glucagon (GCG)- and INS-producing cells. In addition, the expression of the three molecules was evaluated also in relation to different diets.RETN was observed only in the endocrine pancreas, showing a wide distribution throughout the pancreatic islets with few negative cells and the RETN producing cells colocalized with both α cells and ß cells. No differences in distribution and immunostaining intensity of RETN, GCG and INS were observed among the three groups. Quantitative PCR showed the expression of RETN, GCG and INS in all tested samples. No significant differences were observed for RETN and GCG among all three groups of sheep. Instead, a high statistically significant expression of INS was detected in the MxF group with respect to the Exp and MxD groups.These results highlight the localization of RETN in GCG- and INS-secreting cells involved in glucose homeostasis suggesting a modulatory role for RETN. Furthermore, the RETN expression is not influenced by food supplementation and thus is not affected by diet.

DNA Methylation Status of the RETN and ADIPOQ Genes in Sporadic Colon Cancer

DNA Methylation Status of the RETN and ADIPOQ Genes in Sporadic Colon Cancer

Evaluation of resistin, prolactin, and aromatase in women with breast cancer

Cancer is a group of diseases characterized by uncontrolled cell division leading to growth of abnormal tissue, it is a common term for tumors that affect the body's organs, which are the two types of benign tumors and malignant tumors (which are known as carcinoid tumors). A distinction is made between them by examining the tissue (taking a sample). Breast cancer (BC) is formed due to a change in the functioning and growth of cells that make up breast tissue without the ability to control it, which turns them into cancer cells with the ability of these cells to spread. The aims of the study were to evaluate serum levels of resistin (RST), prolactin (PRL), aromatase (ARO), in women with breast cancer and compared with apparently healthy women (control). This study is a cross-sectional, hospital-based study, the protocol of this study was approved by the scientific committee of Tikrit University College of Medicine, and the agreement of the attendance to Kirkuk Oncology Center, Kirkuk general hospital to collect the sample from the patients was approved by the Kirkuk Health Directorate. This study was carried out at the Oncology Center in Kirkuk City-Iraq from the beginning of December 2022 to the end of May 2023. The subject enrolled in the study were divided into (44) breast cancer women and (42) apparently healthy women as control In Kirkuk city. The highest percentage of age for women with BC equal to (34.1%) in the age group (50-59) years, with mean age, was 48.7 years and the statistical tests data obtained showed: highest significant elevation of RST, PRL, and ARO level in women with BC were 6.8±1.8 ng/ml, 58.7±8.4 ng/ml, and 1.5±0.4 pg/ml as compared to control group 4.4±0.5 ng/ml, 24.4±7.2 ng/ml, and 0.4±0.2 pg/ml respectively at (p&lt;0.001). The present study conclude that levels of resistin, prolactin, and aromatase dismutase were significantly higher in women with breast cancer compared to the control.

Increases in BMI contribute to worsening inflammatory biomarkers related to breast cancer risk in women: a longitudinal study.

Inflammatory adipokines and cytokines play a pivotal role in linking obesity and breast cancer (BC) risk in women. We investigated the longitudinal associations between BMI change and trajectories of inflammatory biomarkers related to BC risk. A longitudinal study was conducted among 442 Chinese women with 3-year repeated measures from 2019 to 2021. Plasma circulating inflammatory biomarkers related to BC risk, including adiponectin (ADP), resistin (RETN), soluble leptin receptor (sOB-R), insulin-like growth factor-binding protein-3 (IGFBP-3), and C-reactive protein (CRP), were examined annually. Linear mixed-effect models (LMM) were applied to investigate associations of time-varying BMI with trajectories of biomarkers. We additionally examined the modification effect of baseline BMI groups, menopausal status, and metabolic syndrome. BMI was associated with increased levels of RETN, CRP, sOB-R, and decreased levels of ADP at baseline. An increasing BMI rate was significantly associated with an average 3-year increase in RETN (β = 0.019, 95% CI 0.004 to 0.034) and sOB-R (β = 0.022, 95% CI 0.009 to 0.035), as well as a decrease in ADP (β = - 0.006, 95% CI - 0.012 to 0.001). These associations persisted across different baseline BMI groups. An increasing BMI rate was significantly associated with an average 3-year increase in CRP levels among normal weight (β = 0.045, 95% CI 0.001 to 0.088) and overweight (β = 0.060, 95% CI 0.014 to 0.107) women. As BMI increased over time, a more remarkable decrease in ADP was observed among women with metabolic syndrome (β = - 0.016, 95% CI - 0.029 to - 0.004) than those without metabolic syndrome at baseline. A higher increase rate of BMI was associated with poorer trajectories of inflammatory biomarkers related to BC risk. Recommendations for BMI reduction may benefit BC prevention in women, particularly for those with metabolic syndrome.

Genetic Variants Associated with Acne Vulgaris.

Acne vulgaris (AV) ranks among the common chronic inflammatory disorders that impact the sebaceous components of hair follicles. Acne vulgaris is characterised by cardinal manifestations such as the presence of pimples, nodules, pustules, and cysts, which have the potential to lead to the development of acne scarring and pigmentation. The phenomenon is influenced by polygenic inheritance or can be ascribed to the interplay between multiple genes and environmental factors. In recent years, some researchers have found that some genes (such as IL, TNF, RETN, CYP family, MMPs and TIMPs genes et al) are associated with acne vulgaris and may affect the progression and prognosis of the disease. The number of reviews addressing acne-associated genetic variants, however, is limited. In that case, we have compiled a list of prevalent genes associated with acne in recent times. This helps us understand acne's genetic basis and lets us step in early for people prone to severe acne, lowering the chance of acne scars.

Bioinformatic Analysis and Machine Learning Methods in Neonatal Sepsis: Identification of Biomarkers and Immune Infiltration.

The disease neonatal sepsis (NS) poses a serious threat to life, and its pathogenesis remains unclear. Using the Gene Expression Omnibus (GEO) database, differentially expressed genes (DEGs) were identified and functional enrichment analyses were conducted. Three machine learning algorithms containing the least absolute shrinkage and selection operator (LASSO), support vector machine recursive feature elimination (SVM-RFE), and random forest (RF) were applied to identify the optimal feature genes (OFGs). This study conducted CIBERSORT to present the abundance of immune infiltrates between septic and control neonates and assessed the relationship between OFGs and immune cells. In total, 44 DEGs were discovered between the septic and control newborns. Throughout the enrichment analysis, DEGs were primarily related to inflammatory signaling pathways and immune responses. The OFGs derived from machine learning algorithms were intersected to yield four biomarkers, namely Hexokinase 3 (HK3), Cystatin 7 (CST7), Resistin (RETN), and Glycogenin 1 (GYG1). The potential biomarkers were validated in other datasets and LPS-stimulated HEUVCs. Septic infants showed a higher proportion of neutrophils (p < 0.001), M0 macrophages (p < 0.001), and regulatory T cells (p = 0.004). HK3, CST7, RETN, and GYG1 showed significant correlations with immune cells. Overall, the biomarkers offered promising insights into the molecular mechanisms of immune regulation for the prediction and treatment of NS.

RETN gene polymorphisms interact with alcohol dependence in association with depression.

Previous studies suggest that alcohol dependence is associated with increased risk of depression. The occurrence of depressive symptoms is related to polymorphisms in various genetic regions. This study aimed to investigate the interaction of RETN gene polymorphisms (rs1477341, rs3745368) with alcohol dependence on depressive symptoms in adult male during acute alcohol withdrawal. A total of 429 male adults were recruited in this study. Alcohol dependence was assessed using the Michigan alcoholism screening test (MAST). Depression was assessed using the 20-item self-rating depression scale (SDS). Hierarchical regression analysis was used to evaluate the interaction between genes and alcohol dependence on depression. Region of significance (ROS) test was used to explain the interaction effect. The strong and weak forms of the differential susceptibility and diathesis models were used to determine which fits the data better. Our results showed that MAST scores were significantly positively associated with SDS scores (r = 0.23, p < 0.01) in alcohol-dependent patients during alcohol withdrawal. The interaction between genotype and alcohol dependence was significant (β = -0.14, p < 0.05) in a strong diathesis-stress model. Susceptibility for depression symptoms was associated with alcohol dependence in RETN rs1477341 A carriers. Specifically, those that showed more alcohol dependence and the A allele of RETN rs1477341 exhibited more depression symptoms. However, RETN rs3745368 had no significant interaction with alcohol dependence. The A allele of RETN rs1477341 may correlate with susceptibility to depression symptoms in alcohol-dependent individuals during acute alcohol withdrawal.

Relation of resistin gene variants to resistin plasma levels and altered susceptibility to polycystic ovary syndrome: A case control study.

A role for resistin in the pathogenesis of polycystic ovarian syndrome (PCOS) and related features were described for various ethnicities. As its expression is partly inherited, a role for RETN polymorphisms in regulating resistin levels and PCOS risk was shown, but with varied results. To investigate the association of rs34124816 (-537A>C), rs1862513 (-420C>G), rs3219175 (-358G>A), rs3745367 (+299G>A), rs3745369 (+1263G>C), and rs1423096 (+4965C>T) RETN SNPs with PCOS. Study subjects included 583 women with PCOS, and 713 eumenorrheic women serving as controls. Genotyping was done by real-time PCR. Higher minor allele frequency (MAF) of rs34124816, rs3219175, and rs3745369, and lower MAF of rs1862513 and rs1423096 were seen in PCOS cases. Reduced PCOS risk was found with rs3745367 minor-allele homozygotes and rs1423096 minor-allele homozygotes, while increased risk was linked with rs3745367 heterozygotes, and with rs3745369 heterozygotes and minor-allele homozygotes. While it did not reach statistical significance, serum resistin levels were elevated in PCOS cases than in control women and major-allele homozygotes of rs34124816 and rs1862513, and in rs1423096 minor-allele-containing carriers. Carriage of rs34124816 correlated positively with age and LH, whereas rs1862513 positively and rs3745367 negatively correlated with fasting glucose. Six-locus (rs34124816-rs1862513-rs3219175-rs3745367-rs3745369-rs1423096) haplotype analysis demonstrated a significant reduction in AGGGGG and a marked increase in AGGGCG haplotypes between cases and controls, thus assigning PCOS protective and susceptible nature to these haplotypes, respectively. This study is the first to document the contribution of rs34124816 and rs1423096 RETN variants to the risk of PCOS. The varied association of RETN gene variants with PCOS suggests an ethnic contribution of RETN association with PCOS.

Plasma levels of per- and polyfluoroalkyl substances (PFAS) are associated with altered levels of proteins previously linked to inflammation, metabolism and cardiovascular disease

BackgroundPer- and polyfluoroalkyl substances (PFAS) have been linked to immunotoxic and cardiometabolic effects in both experimental and epidemiological studies, but with conflicting results. AimThe aim of the present study was to investigate potential associations between plasma PFAS levels and plasma levels of preselected proteomic biomarkers previously linked to inflammation, metabolism and cardiovascular disease. MethodsThree PFAS (perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and perfluorohexane sulfonic acid (PFHxS)) were measured by non-targeted metabolomics and 249 proteomic biomarkers were measured by the proximity extension assay (PEA) in plasma from 2,342 individuals within the Epidemiology for Health (EpiHealth) study from Sweden (45–75 years old, 50.6 % men). ResultsAfter adjustment for age and sex, 92% of the significant associations between PFOS concentrations and proteins were inverse (p < 0.0002, Bonferroni-adjusted). The results were not as clear for PFOA and PFHxS, but still with 80% and 64 % of the significant associations with proteins being inverse. After adjustment for age, sex, smoking, education, exercise habits and alcohol consumption, levels of epidermal growth factor receptor (EGFR), and paraoxonase type 3 (PON3) remained positively associated with all three PFAS, while resistin (RETN) and urokinase plasminogen activator surface receptor (uPAR) showed inverse associations with all three PFAS. ConclusionsOur findings imply that PFAS exposure is cross-sectionally linked to altered levels of proteins previously linked to inflammation, metabolism and cardiovascular disease in middle-aged humans.

Variation of Proconvertase 1 and Resistin Gene as Risk Factor for Type II Diabetes Mellitus in Obesity Papua Population

Introduction: Risk factors for type 2 diabetes mellitus (T2DM) include obesity and some genetic factors. Obesity involves mild chronic inflammation that predisposes cells to insulin resistance. Two genes that influence obesity and insulin resistance are Proconvertase-1 (PC-1) and resistin (RETN). PC-1 affects the activation of hormones that regulate satiety and hunger. Resistin is one of the inflammatory factors that influence the occurrence of insulin resistance. This study aimed to determine the influence of polymorphism in the PC-1 gene rs1044498 (C&gt;A) and resistin gene RETN + 299 G&gt;A rs3745367 on the risk of diabetes in obese Papua population. Methods: This study involved 58 obese people with T2DM and 58 obese people without DM. We examined the characteristics of blood pressure, lipid profile and insulin resistance by HOMA-IR. The genes examined were PC-1 rs1044498 (C&gt;A) and RETN+ 299 G&gt;A rs3745367 by the PCR-RFLP method. The relationship of gene variations with biochemical parameters was determined with analysis of variance. The results were considered significantly different if P &lt; 0.05. Results: In this study, parameters of diastolic blood pressure, triglycerides and insulin resistance were higher while high density lipoprotein (HDL) levels were lower and significantly different in the obese with T2DM group compared to the obese only group. The carrier of the A allele in the PC-1 gene rs1044498 was higher in the obese group than the obese with T2DM but not significantly different in biochemical parameters. Carrier of the AA genotype in the RETN gene + 299 G&gt;A rs3745367 had higher triglycerides and HOMA-IR and lower HDL levels significantly different (P&lt;0.05) than other genotypes in the obesity with T2DM group. Conclusion: PC-1 rs1044498 gene was a risk factor for obesity but not for T2DM, while RETN gene rs3745367 was a risk factor for dyslipidemia and diabetes in obese people in the Papua population.