Association of the SH2B1 rs7359397 Gene Polymorphism with Steatosis Severity in Subjects with Obesity and Non-Alcoholic Fatty Liver Disease

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver disease worldwide. Some genetic variants might be involved in the progression of this disease. The study hypothesized that individuals with the rs7359397 T allele have a higher risk of developing severe stages of NAFLD compared with non-carriers where dietary intake according to genotypes could have a key role on the pathogenesis of the disease. SH2B1 genetic variant was genotyped in 110 overweight/obese subjects with NAFLD. Imaging techniques, lipidomic analysis and blood liver biomarkers were performed. Body composition, general biochemical and dietary variables were also determined. The SH2B1 risk genotype was associated with higher HOMA-IR p = 0.001; and Fatty Liver Index (FLI) p = 0.032. Higher protein consumption (p = 0.028), less mono-unsaturated fatty acid and fiber intake (p = 0.045 and p = 0.049, respectively), was also referred to in risk allele genotype. Lipidomic analysis showed that T allele carriers presented a higher frequency of non-alcoholic steatohepatitis (NASH) (69.1% vs. 44.4%; p = 0.006). In the genotype risk group, adjusted logistic regression models indicated a higher risk of developing an advanced stage of NAFLD measured by FLI (OR 2.91) and ultrasonography (OR 4.15). Multinomial logistic regression models showed that risk allele carriers had higher liver fat accumulation risk (RRR 3.93) and an increased risk of NASH (RRR 7.88). Consequently, subjects carrying the T allele were associated with a higher risk of developing a severe stage of NAFLD. These results support the importance of considering genetic predisposition in combination with a healthy dietary pattern in the personalized evaluation and management of NAFLD.

Differences in metabolic and liver pathobiology induced by two dietary mouse models of nonalcoholic fatty liver disease

“…The genetics of NAFLD are complex; however, data linking the role of different dietary components in NAFLD pathobiology is strong [5]. Specific dietary components influence lipid accumulation in the liver and NAFLD progression.…”

Predictive Value of Serum Ferritin in Combination with Alanine Aminotransferase and Glucose Levels for Noninvasive Assessment of NAFLD: Fatty Liver in Obesity (FLiO) Study

“…This morbid condition can lead to nonalcoholic steatohepatitis (NASH), advanced fibrosis, cirrhosis, and finally, hepatocellular carcinoma [5]. Multiple environmental and genetic factors are involved in the onset and progression of NAFLD [6]. Concerning NAFLD treatments, weight loss induced by energy-restricted diets, physical activity promotion, and other lifestyle modifications have exhibited promising results leading to a better hepato-metabolic status [7,8].…”

MAFLD vs. NAFLD: shared features and potential changes in epidemiology, pathophysiology, diagnosis, and pharmacotherapy

“…[ 36 ] Others are associated with the risk of developing obesity, such as ADIPOQ [ 37 ] and SH2B1. [ 38 ] These genes have been reported to be involved in IR, glucose, and lipid homeostasis. [ 39 , 40 ] The shared genes mentioned above indicate that NAFLD might have shared functional mechanisms that are involved in the pathogenesis of T2DM and obesity.…”