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

• Published in: Nutrients Vol. 12; no. 5; p. 1260
• Main Authors: Perez-Diaz-del-Campo, Nuria, Abete, Itziar, Cantero, Irene, Marin-Alejandre, Bertha Araceli, Monreal, J. Ignacio, Elorz, Mariana, Herrero, José Ignacio, Benito-Boillos, Alberto, Riezu-Boj, Jose I., Milagro, Fermín I., Tur, Josep A., Martinez, J. Alfredo, Zulet, M. Angeles
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 29.04.2020; MDPI
• Subjects: Adaptor Proteins, Signal Transducing - genetics; administrative management; Alcohol; Alleles; biomarkers; blood; body composition; Carbohydrates; Cholesterol; Diabetes; Diet; Disease Progression; eating habits; Fatty liver; Fatty Liver - etiology; Fatty Liver - genetics; Female; Food; food intake; frequency; Genetic Association Studies; genetic polymorphism; Genetic Predisposition to Disease; genetic variation; genotype; genotyping; Glycemic index; Hemoglobin; Humans; image analysis; Insulin resistance; Lifestyles; liver; Liver diseases; Male; Manufacturers; Metabolic syndrome; Middle Aged; monounsaturated fatty acids; Non-alcoholic Fatty Liver Disease - etiology; Non-alcoholic Fatty Liver Disease - genetics; nutrients; Obesity; Obesity - etiology; Obesity - genetics; Pathogenesis; Polymorphism; Polymorphism, Genetic; Questionnaires; regression analysis; Risk; Severity of Illness Index; Triglycerides; ultrasonography; Weight control; Spain; NAFLD; polymorphisms; steatosis; obesity; SH2B1
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu12051260

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.