RODRIGO VIEIRA COSTA LIMA
Projetos de Pesquisa
Unidades Organizacionais
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina
2 resultados
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- Hypolactasia is associated with insulin resistance in nonalcoholic steatohepatitis(2016) MAZO, Daniel Ferraz de Campos; MATTAR, Rejane; STEFANO, Jose Tadeu; SILVA-ETTO, Joyce Matie Kinoshita da; DINIZ, Marcio Augusto; DUARTE, Sebastiao Mauro Bezerra; RABELO, Fabiola; LIMA, Rodrigo Vieira Costa; CAMPOS, Priscila Brizolla de; CARRILHO, Flair Jose; OLIVEIRA, Claudia P.AIM To assess lactase gene (LCT)-13910C>T polymorphisms in Brazilian non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) patients in comparison with healthy controls. METHODS This was a transverse observational clinical study with NAFLD patients who were followed at the Hepatology Outpatient Unit of the Hospital das Clinicas, Sao Paulo, Brazil. The polymorphism of lactase non-persistence/ lactase persistence (LCT-13910C>T) was examined by PCR-restriction fragment length polymorphism technique in 102 liver biopsy-proven NAFLD patients (steatosis in 9 and NASH in 93) and compared to those of 501 unrelated healthy volunteers. Anthropometric, clinical, biochemical and liver histology data were analyzed. Continuous variables were compared using the t or Mann-Whitney tests, and categorical data were compared with the Fisher's exact test. Univariate logistic regression and multivariate logistic regression adjusted for gender and age were performed. RESULTS No differences in the LCT-13910 genotype frequencies were noted between the NAFLD patients (66.67% of the patients with steatosis were CC, 33.33% were CT, and none were TT; 55.91% of the patients with NASH were CC, 39.78% were CT, and 4.3% were TT; P = 0.941) and the healthy controls (59.12% were CC, 35.67% were CT, and 5.21% were TT) or between the steatosis and NASH patients. That is, the distribution of the lactase non-persistence/lactase persistence polymorphism (LCT-13910C>T) in the patients with NAFLD was equal to that in the general population. In the NASH patients, the univariate analysis revealed that the lactase nonpersistence (low lactase activity or hypolactasia) phenotype was associated with higher insulin levels (23.47 +/- 15.94 mu U/mL vs 15.8 +/- 8.33 mu U/mL, P = 0.027) and a higher frequency of insulin resistance (91.84% vs 72.22%, P = 0.02) compared with the lactase persistence phenotype. There were no associations between the LCT genotypes and diabetes (P = 0.651), dyslipidaemia (P = 0.328), hypertension (P = 0.507) or liver histology in these patients. Moreover, in the NASH patients, hypolactasia was an independent risk factor for insulin resistance even after adjusting for gender and age [OR = 5.0 (95%CI: 1.35-20; P = 0.017)]. CONCLUSION The LCT-13910 genotype distribution in Brazilian NAFLD patients was the same as that of the general population, but hypolactasia increased the risk of insulin resistance in the NASH patients.
- Association between the CYBA and NOX4 genes of NADPH oxidase and its relationship with metabolic syndrome in non-alcoholic fatty liver disease in Brazilian population(2018) RABELO, Fabiola; STEFANO, Jose Tadeu; CAVALEIRO, Ana Mercedes; LIMA, Rodrigo Vieira Costa; MAZO, DanielFerraz de Campos; CARRILHO, Flair Jose; CORREA-GIANNELLA, Maria Lucia; OLIVEIRA, Claudia P.Background: Oxidative stress has been implicated in the progression of severe forms of non-alcoholic fatty liver disease (NAFLD). NADPH oxidase produces reactive oxygen species. In the present study, we investigated for the first time two single nucleotide polymorphisms (SNPs) in the regulatory region of genes encoding NADPH oxidase 4 (NOX4) and p22phox (CYBA) in NAFLD. Methods: A total of 207 biopsy-proven NAFLD patients [simple steatosis (n =27); nonalcoholic steatohepatitis (NASH) (n =180)] were evaluated. Genomic DNA was extracted from peripheral blood cells, and polymorphisms in CYBA (unregistered) and NOX4 (rs3017887) were determined by direct sequencing of PCR. Results: Associations of CYBA-675 T/A with high-density lipoprotein (HDL) (TT vs TA vs AA; P <0.01) and triglycerides (TGL) (TT vs XA; P < 0.01) were observed only in NASH patients. For polymorphisms in the NOX4 gene, NOX4 (rs3017887) CA + AA genotypes was significant associated with alanine aminotransferase (ALT) (CA + AA vs CC; P=0.02). However, there was no association of SNPs in the CYBA and NOX4 genes encoding the NADPH oxidase system proteins and the presence of NASH. Regarding the clinical results, it was observed that the most advanced degrees of fibrosis occurred in patients diagnosed with type 2 diabetes mellitus (66.9% vs 37.5%, P < 0.01) and those who were more obese (32.2 vs 29.0 kg/m(2), P < 0.01). In addition, serum glucose and insulin levels increased significantly in the presence of NASH. Conclusions: There were associations between the presence of the allele A in the NOX4 SNP and a higher concentration of ALT in the NAFLD population; between the presence of the AA genotype in the polymorphism of the CYBA-675 T/A CYBA gene and a higher level of TGL and lower HDL in NASH patients. The presence of metabolic syndrome was associated with advanced degrees of fibrosis in NAFLD patients.