Risco de polimorfismo genético resistina e doença hepática gordurosa não alcoólica / Resistin gene polymorphism and nonalcoholic fatty liver disease risk

ABSTRACT Background Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease and one of the main global health issues in which liver fat surpasses 5% of hepatocytes without the secondary causes of lipid accumulation or excessive alcohol consumption. Owing to the link between NAFLD and insulin resistance (IR) and obesity and the role of resistin in theses metabolic disorders, we explored the possible association between resistin gene (RETN) variant and NAFLD. Methods A total of 308 unrelated subjects, including 152 patients with biopsy-proven NAFLD and 156 controls were enrolled and genotyped for the RETN gene rs3745367 variant using PCR-RFLP method. Results NAFLD patients had higher liver enzymes, systolic blood pressure (SBP), and diastolic blood pressure (DBP) than the controls (P<0.001). However, we observed no significant difference in genotype and allele frequencies between the cases with NAFLD and the controls for the RETN rs3745367 polymorphism either before or after adjustment for confounding factors including age, BMI, sex, smoking status, SBP, and DBP. Conclusion To our knowledge, this study is the first one that investigated the association between RETN gene rs3745367 variant and biopsy-proven NAFLD. Our findings do not support a role for this gene polymorphism in NAFLD risk in Iranian population; nonetheless, they need to be further investigated in other populations.

RESUMO Contexto: A doença hepática gordurosa não alcoólica (DHGNA) é uma doença hepática crônica e um dos principais problemas de saúde global em que a gordura hepática ultrapassa 5% dos hepatócitos sem as causas secundárias de acúmulo lipídico ou consumo excessivo de álcool. Devido à ligação entre a DHGNA e resistência à insulina (IR) e obesidade e o papel da resistina em distúrbios metabólicos, exploramos a possível associação entre a variante do gene resistina (RETN) e a DHGNA. Metodos Foram selecionados 308 indivíduos não relacionados, incluindo 152 pacientes com DHGNA comprovada por biópsia e 156 controles para a variante do gene RETN rs3745367 usando o método PCR-RFLP. Resultados Pacientes com DHGNA apresentaram enzimas hepáticas mais elevadas, assim como pressão arterial sistólica e pressão arterial diastólica maiores do que os controles (P<0,001). No entanto, não se observou diferença significativa nas frequências genótipo e alelo entre os casos com DHGNA e os controles para o polimorfismo RETN rs3745367 antes ou depois do ajuste para fatores de confusão, incluindo idade, índice de massa corporal, sexo, estado de tabagismo, pressão arterial sistólica e pressão arterial diastólica. Conclusão Para nosso conhecimento, este estudo foi o primeiro que investigou a associação entre a variante do gene RETN rs3745367 e a DHGNA comprovada em biópsia. Nossas descobertas não suportam um papel para este polimorfismo genético no risco DHGNA na população iraniana; no entanto, eles precisam ser mais investigados em outras populações.

Lack of evidence for intermolecular epistatic interactions between adiponectin and resistin gene polymorphisms in Malaysian male subjects

Epistasis (gene-gene interaction) is a ubiquitous component of the genetic architecture of complex traits such as susceptibility to common human diseases. Given the strong negative correlation between circulating adiponectin and resistin levels, the potential intermolecular epistatic interactions between ADIPOQ (SNP+45T > G, SNP+276G > T, SNP+639T > C and SNP+1212A > G) and RETN (SNP-420C > G and SNP+299G > A) gene polymorphisms in the genetic risk underlying type 2 diabetes (T2DM) and metabolic syndrome (MS) were assessed. The potential mutual influence of the ADIPOQ and RETN genes on their adipokine levels was also examined. The rare homozygous genotype (risk alleles) of SNP-420C > G at the RETN locus tended to be co-inherited together with the common homozygous genotypes (protective alleles) of SNP+639T > C and SNP+1212A > G at the ADIPOQ locus. Despite the close structural relationship between the ADIPOQ and RETN genes, there was no evidence of an intermolecular epistatic interaction between these genes. There was also no reciprocal effect of the ADIPOQ and RETN genes on their adipokine levels, i.e., ADIPOQ did not affect resistin levels nor did RETN affect adiponectin levels. The possible influence of the ADIPOQ gene on RETN expression warrants further investigation.

Resistin expression in adipose tissues of diet-induced obese mouse model and its influence on skeletal muscle glucose uptake / 第二军医大学学报

Objective: To investigate the expression of resistin (Retn) gene in the adipose tissues of obese mouse and its influence on the skeletal muscle glucose uptake, in an effort to understand the correlation between obese, resistin, and insulin resistance. Methods: The obese and insulin resistance model was induced with high-fat diet in C57BL/6J mice. Twenty-two weeks later the Lee's index (BMI) and the concentrations of blood glucose and plasma insulin were determined. Glucose tolerance test was carried out to verify the appearance of insulin resistance and the impair to glucose tolerance, with normal mice taken as control. Retn mRNA expression in the adipose tissues of model mice (n=10) and control mice (n=5) was detected by Real-time RT-PCR. The resultant resistin protein was co-cultured with mouse skeletal muscle to assess its influence on glucose uptake. Results: An obese and insulin resistance mouse model was successfully induced with high fat diet. The Retn gene expression in adipose tissues was significantly higher in the obese mice than that in normal control mice (P<0.01). The resultant resistin protein had a significant inhibitory effect on the glucose uptake by skeletal muscle with or without insulin (P<0. 05). Conclusion: It is suggested that the overexpression of Retn gene might be one of the reasons responsible for the decrease of glucose uptake by skeletal muscle and the subsequent insulin resistance in the diet-induced obese mice.

Influence of Retn gene expression on glucose uptake by 3T3-L1 cells and the related mechanism / 第二军医大学学报

Objective:To investigate the influence of high expression of Retn gene on glucose uptake by 3T3-L1 cells and to study its mechanism in inducing insulin resistance.Methods:(1)Radioimmunoassay was used to determine the glucose uptake by 3T3-L1 cells with low-,normal-and high-level Retn expression under basal and insulin-stimulated states.(2)RT-PCR and real-time RT-PCR were used to determine the mRNA levels of several glucose transport proteins in 3T3-L1 cells with different expression of Retn,including insulin receptor substrate-1(IRS-1),phosphatidylinositol 3-kinase(PI-3K),AKT-2,glucose transporter-4(GLUT-4),p38 mitogen-activated protein kinase(p38MAPK),and glycogen synthase kinase-3?(GSK-3?).(Results:) The uptake of glucose decreased with the increase of Retn expression under basal and insulin-stimulated conditions.The mRNA expression of 2 signal protein PI-3K and AKT-2 decreased with the increase of Retn expression;and the expression of GSK-3? and p38MAPK increased with the increase of Retn expression.Conclusion: Resistin protein can induce insulin resistance in adipocytes,which might be related to the expression changes of some proteins in PI-3K and Ras pathways.