Changes in adipokine indicators depending on A1166C polymorphism of the angiotensin II type 1 receptor gene as a predictor of the arterial hypertension.

Objective. Genetic factors substantially contribute to the development and duration of arterial hypertension. The study of the A1166C polymorphism of the angiotensin II type 1 receptor gene (AGTR1) in arterial hypertension is an auspicious area for assessing the relationship between heredity, hypertension development, and adipokines, but it still remains debatable. The purpose of the current study was to investigate serum adipokines levels depending on the AGTR1 A1166C polymorphism. Methods. A total of 86 patients with arterial hypertension were examined, who underwent the evaluation of the allelic A1166C polymorphism of AGTR1 by polymerase chain reaction with electrophoretic detection and determination of serum adipokines levels using enzyme-linked immunosorbent assay. Results. In the group of patients with arterial hypertension, a significant increase in serum adipokines (resistin, adiponectin, and leptin) levels was found against the background of a decrease in the antianorexic hormone ghrelin with a predominance of CC genotype carriers compared with AA genotype carriers of the AGTR1. A statistically significant decrease in ghrelin and an increase in serum adipokines (resistin, adiponectin, and leptin) in CC genotype carriers compared with AA genotype carriers of the AGTR1 were found suggesting that CC genotype carriers may be predictors of the development of arterial hypertension in our patients. Conclusions. Statistically significant decrease in ghrelin and increase in serum adipokines (resistin, adiponectin, and leptin) were found in CC genotype carriers compared with AA genotype carriers of the AGTR1, which suggests that carriers of the CC genotype are predictors of the arterial hypertension development in our patients.

Resistin Gene Promoter -420C>G (rs1862513) and +299 G>A (rs3745367) Polymorphisms in Psoriasis.

BACKGROUND: The pro-inflammatory adipokine resistin is known to be related to obesity, insulin resistance, and inflammation. Resistin's significance in the etiology of inflammatory illnesses, such as psoriasis, is explored herein. We examined the link between resistin gene polymorphisms (-420 C>G and +299 G>A) and psoriasis in the Turkish population. METHODS: In this study, we examined 107 patients with psoriasis and 103 healthy controls. Resistin -420 C>G (rs1862513) and +299 G>A (rs3745367) gene polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: In patients with psoriasis, the frequency of the resistin -420 CG genotype was meaningfully lower than in the controls. In comparison with the controls, the resistin +299 GA genotype and A allele frequencies were significantly higher. The Resistin -420 CG genotype significantly reduced the risk of psoriasis incidence, while the resistin +299 GA genotype and A allele were found to be associated with a higher risk of psoriasis. CONCLUSIONS: In the Turkish community, resistin gene polymorphisms at -420 C>G and +299 G>A may exert an important influence on psoriasis etiology and susceptibility.

The rs1862513 promoter variant of resistin gene influences susceptibility to nonalcoholic fatty liver disease.

OBJECTIVES: Nonalcoholic fatty liver disease is the term used for a range of conditions in which fat builds up in the liver and exceeds 5% of hepatocytes without inordinate alcohol intake or other causes of lipid accumulation. Regarding the fact that insulin resistance and obesity play key roles in the pathogenesis of nonalcoholic fatty liver disease, as well as the connection between resistin and these metabolic diseases, the association between nonalcoholic fatty liver disease and a resistin gene (RETN) polymorphism was examined. METHODS: In this genetic case-control association study, 150 biopsy-proven nonalcoholic fatty liver disease patients and 154 controls were enrolled and genotyped for the RETN rs1862513 (-420C>G) gene polymorphism using PCR-RFLP method. RESULTS: The -420C>G genotype frequency distributions in both groups were consistent with Hardy-Weinberg equilibrium (HWE; p>0.05). The carriers of the RETN -420C>G "CC" genotype compared with the "GG" genotype occurred less frequently in the cases with nonalcoholic fatty liver disease than in the controls, and the difference remained significant even after adjustment for confounding factors (p=0.030; OR=0.47, 95%CI=0.36-0.93). Interestingly, the RETN -420C>G "C" allele was also associated with a decreased risk for nonalcoholic fatty liver disease too (p=0.042; OR=0.72, 95%CI=0.53-0.95). CONCLUSION: We found for the first time an association between biopsy-proven nonalcoholic fatty liver disease and RETN -420C>G promoter polymorphism. The carriers of the RETN -420C>G "CC" genotype had a 53% decreased risk for nonalcoholic fatty liver disease. Our findings, however, need to be corroborated by further studies.

Mendelian randomization analyses reveal no genetic causal effects of major adipokines on systemic lupus erythematosus.

Epidemiological studies have shown that the levels of serum adipokine such as leptin and resistin are associated with the risk of developing systemic lupus erythematosus (SLE). Nevertheless, whether either leptin or resistin has causal impacts on the risk of SLE is still unknown. In this study, two-sample univariable MR analyses and multivariable MR analysis were performed to explore the causal relationships between adipokines and SLE. Additionally, the potential causal effects of SLE on major adipokines were evaluated using reverse MR analyses. The results of inverse-variance weighted (IVW), weighted median, weighted mode and MR‒Egger methods concordantly supported that major adipokines have no causal effects on the risk of SLE. In the multivariable MR IVW analysis with leptin and resistin as covariates, neither leptin (odds ratio (OR) = 3.093, P = 0.067) nor resistin (OR = 0.477, P = 0.311) was identified as an independent risk factor for SLE, which is in line with the univariable MR results. In conclusion, our analyses revealed no evidence to support that these three major adipokines are risk factors for SLE.

Macrophage-derived human resistin promotes perivascular adipose tissue dysfunction in experimental inflammatory arthritis.

Cardiovascular disease (CVD) is the leading cause of death in rheumatoid arthritis (RA). Resistin is an adipokine that induces adipose tissue inflammation and activation of monocytes/macrophages via adenylate cyclase-associated protein-1 (CAP1). Resistin levels are increased in RA and might cause perivascular adipose tissue (PVAT) dysfunction, leading to vascular damage and CVD. This study aimed to investigate the role of resistin in promoting PVAT dysfunction by increasing local macrophage and inflammatory cytokines content in antigen-induced arthritis (AIA). Resistin pharmacological effects were assessed by using C57Bl/6J wild-type (WT) mice, humanized resistin mice expressing human resistin in monocytes-macrophages (hRTN+/-/-), and resistin knockout mice (RTN-/-) with AIA and respective controls. We investigated AIA disease activity and functional, cellular, and molecular parameters of the PVAT. Resistin did not contribute to AIA disease activity and its concentrations were augmented in the PVAT and plasma of WT AIA and hRTN+/-/- AIA animals. In vitro exposure of murine arteries to resistin impaired vascular function by decreasing the anti-contractile effect of PVAT. WT AIA mice and hRTN+/-/- AIA mice exhibited PVAT dysfunction and knockdown of resistin prevented it. Macrophage-derived cytokines, markers of types 1 and 2 macrophages, and CAP1 expression were increased in the PVAT of resistin humanized mice with AIA, but not in knockout mice for resistin. This study reveals that macrophage-derived resistin promotes PVAT inflammation and dysfunction regardless of AIA disease activity. Resistin might represent a translational target to reduce RA-driven vascular dysfunction and CVD.

Interaction effect between low birthweight and resistin gene rs1862513 variant on insulin resistance and type 2 diabetes mellitus in adulthood: Toon Genome Study.

AIMS/INTRODUCTION: Gene-environment interactions are considered to critically influence type 2 diabetes mellitus development; however, the underlying mechanisms and specific interactions remain unclear. Given the increasing prevalence of low birthweight (LBW) influenced by the intrauterine environment, we sought to investigate genetic factors related to type 2 diabetes development in individuals with LBW. MATERIALS AND METHODS: The interaction between 20 reported type 2 diabetes susceptibility genes and the development of type 2 diabetes in LBW (<2,500 g) individuals in a population-based Japanese cohort (n = 1,021) was examined by logistic regression and stratified analyses. RESULTS: Logistic regression analyses showed that only the G/G genotype at the rs1862513 locus of the resistin gene (RETN), an established initiator of insulin resistance, was closely related to the prevalence of type 2 diabetes in individuals with LBW. Age, sex and current body mass index-adjusted stratified analyses showed a significant interaction effect of LBW and the RETN G/G genotype on fasting insulin, homeostatic model assessment 2-insulin resistance, Matsuda index and the prevalence of type 2 diabetes (all P-values for interaction <0.05). The adjusted odds ratio for type 2 diabetes in the LBW + G/G genotype group was 7.33 (95% confidence interval 2.43-22.11; P = 0.002) compared with the non-LBW + non-G/G genotype group. Similar results were obtained after excluding the influence of malnutrition due to World War II. CONCLUSIONS: Simultaneous assessment of LBW and the RETN G/G genotype can more accurately predict the risk of future type 2 diabetes than assessing each of these factors alone, and provide management strategies, including early lifestyle intervention in LBW population.

GHRL, LEP, LEPR genes polymorphism and their association with the metabolic syndrome in the Ukrainian population.

Objective. Many conflicting results have been obtained in the study of leptin (LEP) and leptin receptor (LEPR) gene variants that are associated with the obesity and diabetes possibly due to differences in the study populations. The aim of this study was to evaluate changes in the metabolic hormones (leptin, ghrelin, adiponectin, resistin) levels in the blood of obese patients in relation to the GHRL (rs696217), LEP (rs7799039), LEPR (rs1137100, rs1137101, rs1805094) polymorphism in Ukrainian population. Methods. The study involved 53 obesity cases and 48 non-obesity subjects (controls). The GHRL, LEP, and LEPR genes polymorphism (rs696217, rs7799039, rs1137100, rs1137101, rs1805094) was genotyped using a TaqMan real-time polymerase chain reaction method. Blood hormones (leptin, ghrelin, adiponectin, resistin) were determined with commercially available kits using a Multiskan FC analyzer. Results. The study of the effect of genotypes of the GHRL (rs696217), LEP (rs7799039), and LEPR (rs1137100, rs1805094) polymorphisms on the level of metabolic hormones (leptin, ghrelin, adiponectin, resistin) in the blood of obese patients did not show reliably significant results. Thus, the presence of the LEPR genes (rs1137101) polymorphism in the Ukrainian population indicates an increased risk of the metabolic syndrome development regardless of the homozygous or heterozygous genotype (genotypes AA, AG, GG). Conclusions. We established a significant effect of the presence of the A allele and G allele of the LEPR gene polymorphism (rs1137101) on the level of leptin, ghrelin, adiponectin, and resistin in the serum of patients diagnosed with the metabolic syndrome in the Ukrainian population.

Study on the correlation between gene polymorphisms of adiponectin and resistin levels and abdominal aortic aneurysm.

OBJECTIVES: Abdominal Aortic Aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. This study aimed to examine the potential association of the +276G/T and -420C>G polymorphisms in the resistin gene with AAA susceptibility and progression. METHOD: We performed a retrospective study involving AAA patients and healthy controls, assessing the distribution of the +276G/T and -420C>G genotypes in both groups. Hardy-Weinberg equilibrium was assessed for both polymorphisms. Logistic regression was used to explore the influence of these genotypes on AAA occurrence and progression, adjusting for relevant confounders. RESULTS: The distribution of +276G/T polymorphism did not significantly differ between AAA patients and controls. Conversely, a significant difference was observed in the genotype distribution of -420C>G polymorphism between the two groups. The CC genotype and CC/CG genotypes of -420C>G polymorphism were found to be associated with an increased risk and progression of AAA. CONCLUSIONS: The -420C>G polymorphism, particularly the CC genotype and CC/CG genotypes, might play a substantial role in AAA susceptibility and progression. The present findings underscore the need for further investigations to confirm these associations and fully elucidate the role of the resistin gene in AAA.

Integrated Analyses of Single-Cell Transcriptome and Mendelian Randomization Reveal the Protective Role of Resistin in Sepsis Survival in Intensive Care Unit.

The high morbidity and mortality rates associated with sepsis highlight the challenges of finding specific remedies for this condition in the intensive care unit (ICU). This study aimed to explore the differentially expressed genes (DEGs) specific to cell types in sepsis and investigate the role of resistin in the survival of sepsis patients through Mendelian randomization (MR) analyses. We used single-cell and bulk transcriptome data to identify cell type-specific DEGs between sepsis and healthy controls. MR analyses were then conducted to investigate the causal relationships between resistin (one of the identified DEGs) levels and the survival of sepsis patients. Additionally, we utilized meQTL (methylation quantitative trait loci) to identify cytosine-phosphate-guanine (CpG) sites that may directly affect sepsis. We identified 560 cell type-specific DEGs between sepsis and healthy controls. Notably, we observed the upregulation of resistin levels in macrophages during sepsis. In bulk transcriptome, RETN is also upregulated in sepsis samples compared with healthy controls. MR analyses revealed a negative association existed between the expression of resistin, at both gene and protein levels, and the mortality or severity of sepsis patients in ICU. Moreover, there were no associations observed between resistin levels and death or organ failure due to other causes. We also identified three methylation CpG sites, located in RETN or its promoter region-cg06633066, cg22322184, and cg02346997-that directly affected both resistin protein levels and sepsis death in the ICU. Our findings suggest that resistin may provide feasible protection for sepsis patients, particularly those with severe cases, without serious side effects. Therefore, resistin could be a potential drug candidate for sepsis treatment. Additionally, we identified two CpG sites, cg06633066 and cg22322184, that were associated with RETN protein levels and sepsis death, providing novel insights into the underlying mechanisms of sepsis.

Genetic Association of Circulating Adipokines with Risk of Idiopathic Pulmonary Fibrosis: A Two-Sample Mendelian Randomization Study.

PURPOSE: The causal relationships between circulating adipokines and idiopathic pulmonary fibrosis (IPF) are yet to be established. We performed a two-sample Mendelian randomization (MR) study to investigate the causal roles of adipokines on IPF risk. METHODS: We analyzed the summary data from genome-wide association studies (GWAS), including adiponectin, leptin, resistin and monocyte chemoattractant protein-1 (MCP-1) and IPF. The inverse-variance weighted (IVW) method was considered as the major method and the MR-Egger, weighted median, simple mode and weighted mode were utilized as complementary methods. We also performed the sensitivity analyses, including heterogeneity test, horizontal pleiotropy test and leave-one-out analysis. RESULTS: The selected number of single nucleotide polymorphisms (SNPs) was 13 for adiponectin, 6 for leptin,12 for resistin, and 6 for MCP-1, respectively. The results showed a causal effect of the circulating adiponectin levels on the risk of IPF (OR 0.645, 95% CI 0.457-0.911, P = 0.013). However, we did not observe significant associations of genetic changes in serum leptin (OR 1.018, 95% CI 0.442-2.346, P = 0.967), resistin (OR 1.002, 95% CI 0.712-1.408, P = 0.993), and MCP-1 (OR 1.358, 95% CI 0.891-2.068, P = 0.155) with risk of developing IPF. There was no evidence of heterogeneity or horizontal pleiotropy. The sensitivity analyses confirmed that our results were stable and reliable. CONCLUSIONS: The increase in serum adiponectin was associated causally with a decreased risk of developing IPF. There is no evidence to support a causal association between leptin, resistin or MCP-1 with risk of IPF. Further studies are needed to confirm our findings.

Genetically determined circulating resistin concentrations and risk of colorectal cancer: a two-sample Mendelian randomization study.

PURPOSE: Resistin, a novel pro-inflammatory protein implicated in inflammatory processes, has been suggested to play a role in colorectal development. However, evidence from observational studies has been inconsistent. Mendelian randomization may be a complementary method to examine this association. METHODS: We conducted a two-sample Mendelian randomization to estimate the association between genetically determined circulating resistin concentrations and risk of colorectal cancer (CRC). Protein quantitative trait loci (pQTLs) from the SCALLOP consortium were used as instrumental variables (IVs) for resistin. CRC genetic summary data was obtained from GECCO/CORECT/CCFR (the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry), and FinnGen (Finland Biobank). The inverse variance weighted method (IVW) was applied in the main analysis, and other robust methods were used as sensitivity analyses. Estimates for the association from the two data sources were then pooled using a meta-analysis approach. RESULTS: Thirteen pQTLs were identified as IVs explaining together 7.80% of interindividual variation in circulating resistin concentrations. Based on MR analyses, genetically determined circulating resistin concentrations were not associated with incident CRC (pooled-IVW-OR per standard deviation of resistin, 1.01; 95% CI 0.96, 1.06; p = 0.67. Restricting the analyses to using IVs within or proximal to the resistin-encoding gene (cis-IVs), or to IVs located elsewhere in the genome (trans-IVs) provided similar results. The association was not altered when stratified by sex or CRC subsites. CONCLUSIONS: We found no evidence of a relationship between genetically determined circulating resistin concentrations and risk of CRC.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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 (ß = -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. CONCLUSIONS: 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.

BACKGROUND: 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. AIM: 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. METHODS: Study subjects included 583 women with PCOS, and 713 eumenorrheic women serving as controls. Genotyping was done by real-time PCR. RESULTS: 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. CONCLUSIONS: 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.

Adipokines and risk of rheumatoid arthritis: A two-sample multivariable Mendelian randomisation study.

Adiponectin, leptin, and resistin are thought to be involved in the pathogenesis of rheumatoid arthritis (RA). However, the causal relationship between these adipokines and the risk for RA is unclear. We performed a range of two-sample Mendelian randomisation (MR) analyses to assess the causal effect of circulating adiponectin, leptin, and resistin on RA risk in European and East Asian individuals. Different sets of adiponectin-, leptin-, and resistin-related genetic variants were used as instruments for genetically determined adipokine levels. As body mass index (BMI) is a risk factor for RA and affects adipokine levels, multivariable MR was used to calculate the causal effect of each adipokine on RA risk taking BMI into account. Several MR analyses revealed no evidence of a causal relationship between circulating adiponectin, leptin, or resistin levels and RA risk in either Europeans or East Asians. Similarly, multivariable MR did not provide evidence of any causal effect of adiponectin, leptin, or resistin on RA risk when taking BMI into account. This MR study shows for the first time that genetically determined levels of adiponectin, leptin, or resistin do not have a direct causal effect on the risk of developing RA after adjustment for BMI.

The identification of a novel SNP in the resistin (RETN) gene associated with growth traits in Karakul and Awassi sheep.

Resistin is one of the most important adipocytokines in mammalian cells due to its involvement in insulin resistance, obesity, and autoimmune diseases. Resistin is encoded by RETN gene that is primarily expressed in adipose tissues. Mutations in this gene have been associated with several productive traits in animals. This study was conducted to assess the possible biomarker capacity of RETN by evaluating its association with growth traits in two economically important sheep in the Middle East. Genotyping was conducted using PCR-single strand conformation polymorphism (SSCP), and the polymorphism of RETN was associated with several growth traits for three months intervals starting from birth until one year of age. In a total of 190 Karakul sheep and 245 Awassi sheep, only one SNP (233A > C) was detected in the RETN gene. The identified novel SNP showed significant associations with all growth traits at the ages of six, nine, and twelve months. At the age of six months onward, lambs with AC and CC genotypes showed respectively lower body weight and length, chest and abdominal circumferences, and wither and rump heights than those with AA genotype. Due to the remarkable association between RETN;233A > C and lower growth traits, this genotype is suggested as a promising marker to assess growth traits in Karakul and Awassi sheep. This is the first study that demonstrated the importance of RETN as a possible tool for evaluating growth traits in two breeds of sheep with a possibility to be applied to other breeds via large-scale association analysis.

Impacts of RETN genetic polymorphism on breast cancer development in Beni-Suef females, Egypt.

Breast cancer is the most common cancer among females with increasing incidence and death rates. Resistin is pro-inflammatory molecule which shares in diverse cellular signaling pathways. This study aimed to evaluate resistin and RETN rs3219175 gene polymorphism and their relevance to diagnostic susceptibility, prognostic value, and genetic risk among Egyptian female patients with breast cancer. Eighty female patients with breast cancer were recruited from the Oncology Department, Faculty of Medicine, Beni-Suef University. Breast cancer staging and grading were determined. Eighty age-matched normal females participated as controls. Quantitative determination of serum resistin was assayed by an enzyme-linked immunosorbent assay (ELISA). RETN rs3219175 gene polymorphism was determined by real time polymerase chain reaction (RT-PCR) TaqMan allelic discrimination assay. Serum resistin showed statistically significantly higher level among females with breast cancer when compared to controls (p < 0.001). Resistin showed sensitivity of 80% and specificity of 67.5% at cut off value of 1.27 ng/mL for diagnosis of breast cancer (p =0.001). RETN rs3219175 gene polymorphism showed significantly higher frequency of AG, AA genotypes, and A allele among cases when compared to controls (p < 0.001). No statistical difference was found in resistin level or RETN rs3219175 gene polymorphism regarding tumor characteristics including size, lymph nodes or distant metastasis. Resistin showed significantly higher level among carriers of AG followed by AA genotypes and among A allele (p < 0.001). In conclusion, resistin could be proposed as a possible potential diagnostic marker and A allele of RETN rs3219175 gene might be suggested as a genetic risk allele among female patients with breast cancer.

Resistin G-A haplotype at SNP-420/-358 is associated with the latent sarcopenic obesity index in the toon genome study.

AIM/INTRODUCTION: Resistin, which induces insulin resistance, is mainly expressed in monocytes/macrophages in humans. We reported previously that serum resistin was highest in the G-A haplotype defined by resistin single nucleotide polymorphisms (SNPs) at -420 (rs1862513) and - 358 (rs3219175). As sarcopenic obesity is associated with insulin resistance, we aimed to examine whether serum resistin and its haplotypes were associated with sarcopenic obesity at a latent stage. MATERIALS AND METHODS: We cross-sectionally analyzed 567 community-dwelling Japanese participants attending annual medical check-ups in which the sarcopenic obesity index was evaluated. The age- and gender-matched normal glucose tolerance subjects with G-A homozygotes and those with C-G homozygotes were examined via RNA-sequencing and pathway analysis (each n = 3), and RT-PCR (each n = 8). RESULTS: In multivariate logistic regression analyses, the fourth quartile (Q4) of serum resistin and G-A homozygotes were both associated with the latent sarcopenic obesity index defined by a visceral fat area of ≥ 100 cm2 and grip strength Q1 after adjustment for age and gender, with or without other confounding factors. RNA sequencing and pathway analysis showed that tumor necrosis factor (TNF) was involved in the top five pathways in the whole blood cells of G-A homozygotes compared with C-G homozygotes. RT-PCR revealed that TNF mRNA was higher in G-A homozygotes than in C-G homozygotes. CONCLUSIONS: The G-A haplotype was associated with the latent sarcopenic obesity index defined by grip strength in the Japanese cohort, could be mediated by TNF-α.

Upregulation of peripheral blood mononuclear cells resistin gene expression in severe obstructive sleep apnea and obstructive sleep apnea with coexisting type 2 diabetes mellitus.

PURPOSE: Obstructive sleep apnea (OSA) is characterised by increased systemic inflammation, and is often accompanied with type 2 diabetes mellitus (T2DM) and cardiovascular disease. The aim of this investigation was to evaluate gene expression of resistin, its receptor CAP1 and CD36 as the indicators of the inflammatory changes in PBMCs in relation to the severity of OSA, and the presence of type 2 diabetes mellitus (T2DM) in OSA. METHODS: Severity of OSA was defined by the apnea/hypopnea index (AHI): AHI < 30: mild to moderate OSA (MM-OSA), AHI ≥ 30: severe OSA (S-OSA). Presence of T2DM was captured: OSA with T2DM (OSA + T2DM), OSA without T2DM (OSA-T2DM). PBMC resistin, CAP1, and CD36 mRNA were determined by real-time PCR. RESULTS: Resistin mRNA was significantly upregulated in S-OSA (N = 54) compared to the MM-OSA (N = 52, P = 0.043); CAP1 and CD36 mRNA levels did not differ between the groups (P = 0.302; P = 0.166, respectively). Resistin mRNA was significantly upregulated in OSA + T2DM (N = 29) compared to the OSA-T2DM (N = 77, P = 0.029); CAP1 and CD36 mRNA levels did not differ between the groups (P = 0.662; P = 0.108, respectively). AHI and T2DM were independent predictors of resistin mRNA above the 75th percentile (OR = 3.717 [1.152-11.991]; OR = 3.261 [1.000-10.630], P = 0.042 respectively). CONCLUSION: Resistin gene upregulation in S-OSA indicates its possible contribution to increased inflammation in S-OSA and makes it a possible marker of the disease severity. Resistin gene upregulation in OSA + T2DM suggests that a joint effect of these two comorbidities may have a major contribution to increased inflammation and complications that arise from this state.

Role of resistin (rs7139228) gene polymorphism with metabolic response after a hypocaloric mediterranean diet.

BACKGROUND: The SNP (rs7139228) of the RETN gene is a polymorphism that has been associated with metabolic disorder in subjects with obesity, and its effect on metabolic response after dietary intervention has not been evaluated. OBJECTIVE: Our objective was to analyse the effects of the polymorphism of the RETN gene rs7139228 on metabolic changes secondary to weight loss with a hypocaloric Mediterranean diet. DESIGN: 1000 obese Caucasian patients were evaluated. An anthropometric evaluation and a biochemical analysis were performed before and after 12 weeks of a hypocaloric Mediterranean diet. The statistical analysis was performed as a dominant model (GG vs GA+AA). RESULTS: Improvements in anthropometric parameters, leptin levels and systolic blood pressure were similar in both genotype groups. In non- A allele carriers, levels of resistin, insulin, HOMA-IR, triglycerides and C-reactive protein decreased. The improvements were statistically significant in this group; resistin (-1.3+0.1ng/dL: p=0.02), triglycerides (-22.9+4.9mg/dl: p=0.02), CRP (-2.7+0 0.4mg/dl: p=0.02), insulin -6.5+1.8 mIU/L: p=0.02) and HOMA-IR (-2.2+0.8: p=0, 03). In addition, insulin, HOMA-IR and resistin levels were higher in A allele carriers than in non-carriers. Finally, the prevalence of metabolic syndrome and hyperglycaemia were higher in A allele carriers, and these percentages only decreased after intervention in non-A allele carriers. CONCLUSION: The A rs7139228 allele is associated with a worse metabolic response (insulin, HOMA-IR, triglycerides and CRP) after weight loss with a hypocaloric Mediterranean diet. A non-significant decrease in the prevalence of metabolic syndrome and hyperglycaemia were detected in A allele carriers.