A case–control study on the effect of metabolic gene polymorphisms, nutrition, and their interaction on the risk of non-alcoholic fatty liver disease

Abstract

The oxidative stress is a key issue in the etiology of non-alcoholic fatty liver disease (NAFLD). The aim of our study was to evaluate the effect of metabolic gene polymorphisms involved in the oxidative stress (GSTT1, GSTM1, SULT1A1, CYP2E1, and 1A1), lifestyle and nutrition aspects, and their interaction, on the risk of NAFLD. We enrolled 294 cases and 359 controls, and collected demographics, anthropometric, lifestyle, and nutrition data. A subgroup of NAFLD provided additional data on nutrients and on physical activity engagement. Each patient provided a blood sample for DNA extraction and genotyping. Clinical and laboratory data were collected from cases. Multivariable analysis shows a significant protective effect of age, gender, and moderate drinking habits on the risk of NAFLD, while an increased risk for greater consumption of fruit and grilled meat or fish. Significant interactions were reported between alcohol consumption, fruit intake, grilled meat and fish, and selected genetic variants. From the subgroup analysis, a moderate/high consumption of fat and/or grilled meat/fish, and a high consumption of white meat increase the risk of NAFLD. Engaging any physical activity at least 1 time/ week halves the risk of NAFLD. Besides confirming the beneficial effect of moderate alcohol intake and regular physical activity, and the increased risk associated with high fruit and fat intake, for the first time, we report a detrimental effect of grilled food on NAFLD risk. An effect modification by selected gene variants increases the risk in combination with fruit and grilled food intake.

Dietary patterns are associated with the risk of non-alcoholic fatty liver disease among Iranian population: A case-control study

“…However, Chung et al did not find a relationship between the high carbohydrate diet and the risk of NAFLD (33). Our findings confirm the result of the studies suggesting that a high fruit diet is associated with NAFLD (34,35). Fruits are rich in simple carbohydrates particularly fructose.…”

Dietary patterns are associated with prevalence of fatty liver disease in adults

“…Our findings confirm those of a recent case-control study, which reported an increased risk of NAFLD with greater consumption of fruit. 20 Higher risk of NAFLD due to fruits as well as sugared beverages and snacks may be due to the fact that these foods contain large amounts of sugars, such as fructose and sucrose, which have been associated with the pathophysiology of NAFLD; one study has suggested that NAFLD might result from the potential role of fructose in liver de novo lipogenesis and hepatic inflammation. 21,22 We also observed that modest alcohol consumption is associated with decreased prevalence of NAFLD in males, whereas the high-carbohydrate/ sweet pattern has high factor loadings of alcoholic drinks and is associated with increased NAFLD in females.…”

Nutrition and Genetics in NAFLD: The Perfect Binomium

“…In 2014, Miele et al conducted for the first time a case-control study on the effect of metabolic gene polymorphisms, nutrition and their interaction on the risk of NAFLD in 294 Italian cases and 359 controls [88]. These authors reported that young adults and males display an increased risk of NAFLD, as well as those subjects which consume an unbalanced diet.…”

“…Therefore, the authors examined the interaction between dietary factors and inherited variants in genes that exert key roles as antioxidant defense, such as glutathione S-transferase Mu 1 (GSTM1), glutathione S-transferase theta 1 (GSTT1), cytochrome P450 superfamily members and sulfotransferase 1A1 (SULT1A1). They found that these inherited factors significantly interact with high fruit intake (more than two fruits/day) or high grilled meat/fish consumption (more than once per week), exasperating the risk of developing NAFLD and suggesting a possible role of aromatic hydrocarbons in liver steatosis [88].…”