RESUMO
ABSTRACT Background: Recent studies show an increase in nonalcoholic fatty liver disease (NAFLD) in populations with higher consumption of red meat, processed and cooked at high temperatures. On the other hand, the single nucleotide polymorphism rs738409 in the Patatin-like phospholipase domain containing 3 (PNPLA3) gene has been implicated in susceptibility to NAFLD and liver fibrosis. However, the synergistic effect between red meat consumption and the PNPLA3 gene polymorphism in NAFLD has not yet been evaluated. Objective: To evaluate the association between the presence of the polymorphism in the PNPLA3 gene and the consumption of macronutrients, including meat consumption and its cooking method among NAFLD patients. Methods: This was a cross-sectional study with 91 patients diagnosed with NAFLD by liver biopsy with genotyping for the polymorphism in the PNPLA3 gene were included. The consumption of calories and macronutrients was verified using the semi-quantitative food frequency questionnaire and the specific questionnaire on meat consumption. PNPLA3 gene polymorphism was analyzed by real-time polymerase chain reaction (RT-PCR) and anthropometric evaluation was realized. Results: The mean BMI was 32.38±4.58 kg/m² and the waist circumference was 107±10 cm. On liver biopsy, 42% of patients had significant fibrosis (F≥2). The odds ratio of F≥2 was 2.12 for the GG group and 1.54 for the CG group, compared to the CC group. The mean caloric intake was 1170±463.20 kcal/d. The odds ratio in the CC group concerning high red meat consumption in comparison to low consumption was 1.33. For white meat, the odds ratio was 0.8 when comparing high and low intake, also in the CC group. Conclusion: High red meat intake and PNPLA3 gene polymorphism seem to synergistically affect NAFLD and liver fibrosis, requiring confirmation in a larger number of patients and in different populations.
RESUMO Contexto: Estudos recentes mostram um aumento da doença hepática gordurosa não alcoólica (DHGNA) em populações com maior consumo de carne vermelha, processada e cozida em altas temperaturas. Por outro lado, o polimorfismo rs738409 no gene Patatin-like fosfolipase contendo 3 (PNPLA3) tem sido implicado na suscetibilidade à DHGNA e fibrose hepática. No entanto, o efeito sinérgico entre o consumo de carne vermelha e o polimorfismo no gene PNPLA3 na DHGNA ainda não foi avaliado. Objetivo: Avaliar a associação entre a presença do polimorfismo no gene PNPLA3 e o consumo de macronutrientes, incluindo o consumo de carne e seu modo de cozimento em pacientes com DHGNA. Métodos: Realizamos um estudo transversal com 91 pacientes diagnosticados com DHGNA por biópsia hepática e genotipados para o polimorfismo no gene PNPLA3. O consumo de calorias e macronutrientes foi verificado por meio do questionário de frequência alimentar semi-quantitativo (QFA) e do questionário específico sobre consumo de carnes. O polimorfismo no gene PNPLA3 foi analisado por reação em cadeia da polimerase em tempo real (RT-PCR) e a avaliação antropométrica foi realizada. Resultados: O índice de massa corporal médio foi de 32,38±4,58 kg/m² e a circunferência da cintura foi de 107±10 cm. Na biópsia hepática, 42% dos pacientes apresentavam fibrose significativa (F≥2). O odds ratio de F≥2 foi de 2,12 para o grupo GG e 1,54 para o grupo GC, comparado ao grupo CC. A ingestão calórica média foi de 1.170±463,20 kcal/d. O odds ratio para alto consumo de carne vermelha no grupo CC em comparação ao baixo consumo foi de 1,33. Para a carne branca, este valor foi de 0,8 ao comparar o alto e o baixo consumo, também no grupo CC. Conclusão: A alta ingestão de carne vermelha e o polimorfismo no gene PNPLA3 parecem afetar sinergicamente a DHGNA e a fibrose hepática, necessitando de confirmação em maior número de pacientes e em diferentes populações.
RESUMO
Background and Aim: Non-alcoholic fatty liver disease (NAFLD) is a multifactorial disorder with combination of environmental, genetic and metabolic factors that play role in the progression of disease. This study is aimed to explore the familial clustering of NAFLD among the family members of NASH cirrhotic patients and the association of insulin resistance, metabolic syndrome and genetic polymorphism with the familial clustering. Methods: This cross-sectional observational study included 50 NASH cirrhosis patient and 81 1st degree relatives. Family members were screened for fatty liver by ultrasonogram. Insulin resistance, metabolic syndrome, PNPLA3 and staging of liver stiffness by fibroscan were done. Results: Among 81 family members 47 (58.02%) were found having fatty liver. Of these 14(17.28%) had significant fibrosis. PNPLA3 polymorphism was higher (80.85%) in fatty liver group than (55.9%) without fatty liver groups. Sons (57.89%) and daughters (51.6%) were affected by fatty liver equally. Multivariate logistic regression analysis revealed that a subject with TG>150 mg/dl had 6.159 times increase in odds having NAFLD. A subject with PNPLA3 polymorphism had 3.33 times increase in odds having NAFLD. A subject with HOMA-IR >1.6 had 4.375 times increase in odds having NAFLD. Conclusion: This study indicates that there is a strong familial clustering of NAFLD along with significant fibrosis among the family members of NASH cirrhosis patients. This findings warrants screening for NAFLD among the family members of NASH cirrhosis patients especially with PNPLA3 polymorphism.
RESUMO
Objective To explore the SNP effects ofpatatin-like phospholipase domain which containing 3 (PNPLA3),transmembrane 6 superfamily member 2 (TM6SF2) gene,environmental effects of smoking,alcohol drinking and interaction between gene-gene,gene-environment and drinking-smoking on hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC).Methods We collected anticoagulant peripheral blood from patients of HBV-HCC,chronic hepatitis B (CHB),liver cirrhosis (LC) and from healthy controls to detect the single nucleotide polymorphism (SNP) of patatin-like phospholipase domain containing 3 (PNPLA3) gene loci rs738409 and transmembrane 6 superfamily member 2 (TM6SF2) gene loci rs58542926,using the flight mass spectrometry method.The optimal assignment value of gene polymorphisms was defined by using the online SNP stats.Hardy-Weinberg (H-W) balance was tested for SNP.Effects of the genetic and environmental factors to HBV-HCC were analyzed by using the multiple classification logistic regression method.The gene-gene,gene-smoking and alcohol drinking interaction effects were investigated by Fork-Life analysis and binary logistic regression methods.Results The frequency distribution of CHB group rs738409 loci seemed not in conformity with the H-W balance (x2=11.980,P＜0.005).Two loci frequency distributions in the other groups were all in accordandce with the H-W balance.After adjusting for influences on age and sex and comparing to the healthy group,the rs58542926 mutation appeared as OR=1.659,95％CI:1.026-2.684,P=0.039,in the HBV-HCC group.When comparing to CHB group,the HBV-HCC group presented that drinking as OR=1.680,95％CI:1.121-2.519,P=0.012.When comparing to the LC group,the ORs of drinking and smoking were 1.539 (1.071-2.213) and 1.453 (1.005-2.099) respectively,in the HBV-HCC group.When comparing to the CHB + LC group,interactions between the HBV-HCC group were found rs738409 and rs58542926 on additive model OR=1.548 (U=1.885,P=0.029) and OR=1.658 (P=0.024) on logistic regression model while drinking was rs738409 on interaction additive model with OR=1.811(U=1.965,P=0.024).As for drinking and mutation of rs738409,the multiplication model of logistic regression showed no statistically significant differences.Interaction between smoking and drinking appeared as OR=1.756 (P＜0.001) in the logistics regression multiplication model.Conclusions Factors as mutation of TM6SF2,smoking and drinking all appeared as risk factors for HBV-HCC.Mutations of both PNPLA3 and TM6SF2,together with smoking and drinking all served as risk factors for HBV-HCC.However,the mutation of single PNPLA3 appeared as a protective factor on HBV-HCC.
RESUMO
Objective To explore the SNP effects ofpatatin-like phospholipase domain which containing 3 (PNPLA3),transmembrane 6 superfamily member 2 (TM6SF2) gene,environmental effects of smoking,alcohol drinking and interaction between gene-gene,gene-environment and drinking-smoking on hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC).Methods We collected anticoagulant peripheral blood from patients of HBV-HCC,chronic hepatitis B (CHB),liver cirrhosis (LC) and from healthy controls to detect the single nucleotide polymorphism (SNP) of patatin-like phospholipase domain containing 3 (PNPLA3) gene loci rs738409 and transmembrane 6 superfamily member 2 (TM6SF2) gene loci rs58542926,using the flight mass spectrometry method.The optimal assignment value of gene polymorphisms was defined by using the online SNP stats.Hardy-Weinberg (H-W) balance was tested for SNP.Effects of the genetic and environmental factors to HBV-HCC were analyzed by using the multiple classification logistic regression method.The gene-gene,gene-smoking and alcohol drinking interaction effects were investigated by Fork-Life analysis and binary logistic regression methods.Results The frequency distribution of CHB group rs738409 loci seemed not in conformity with the H-W balance (x2=11.980,P＜0.005).Two loci frequency distributions in the other groups were all in accordandce with the H-W balance.After adjusting for influences on age and sex and comparing to the healthy group,the rs58542926 mutation appeared as OR=1.659,95％CI:1.026-2.684,P=0.039,in the HBV-HCC group.When comparing to CHB group,the HBV-HCC group presented that drinking as OR=1.680,95％CI:1.121-2.519,P=0.012.When comparing to the LC group,the ORs of drinking and smoking were 1.539 (1.071-2.213) and 1.453 (1.005-2.099) respectively,in the HBV-HCC group.When comparing to the CHB + LC group,interactions between the HBV-HCC group were found rs738409 and rs58542926 on additive model OR=1.548 (U=1.885,P=0.029) and OR=1.658 (P=0.024) on logistic regression model while drinking was rs738409 on interaction additive model with OR=1.811(U=1.965,P=0.024).As for drinking and mutation of rs738409,the multiplication model of logistic regression showed no statistically significant differences.Interaction between smoking and drinking appeared as OR=1.756 (P＜0.001) in the logistics regression multiplication model.Conclusions Factors as mutation of TM6SF2,smoking and drinking all appeared as risk factors for HBV-HCC.Mutations of both PNPLA3 and TM6SF2,together with smoking and drinking all served as risk factors for HBV-HCC.However,the mutation of single PNPLA3 appeared as a protective factor on HBV-HCC.
RESUMO
BACKGROUND/AIMS: It is important to determine the noninvasive parameters of histological features in nonalcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the value of genetic variations as surrogate markers of histological features. METHODS: The parameters that affected the histological features of NAFLD were investigated in 211 Japanese patients with biopsy-proven NAFLD. The relationships between genetic variations in PNPLA3 rs738409 or TM6SF2 rs58542926 and histological features were analyzed. Furthermore, the impact of genetic variations that affected the pathological criteria for the diagnosis of nonalcoholic steatohepatitis (NASH) (Matteoni classification and NAFLD activity score) was evaluated. RESULTS: The fibrosis stage of PNPLA3 GG was significantly more progressive than that of CG by multiple comparisons. Multivariate analysis identified PNPLA3 genotypes as predictors of fibrosis of stage 2 or more, but the impact tended to decrease at stage 3 or greater. There were no significant differences among the histological features of the three genotypes of TM6SF2. PNPLA3 genotypes partly affected the definition of NASH by the NAFLD activity score, but TM6SF2 genotypes did not affect the definition of NASH. CONCLUSIONS: In Japanese patients with biopsy-proven NAFLD, PNPLA3 genotypes may partly affect histological features, including stage of fibrosis, but the TM6SF2 genotype does not affect histological features.