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Genome-wide association studies have identified several genetic variants associated with nonalcoholic fatty liver disease. To emphasize metabolic abnormalities in fatty liver, metabolic (dysfunction)-associated fatty liver disease (MAFLD) has been introduced; thus, we aimed to investigate single-nucleotide polymorphisms related to MAFLD and its subtypes. A genome-wide association study was performed to identify genetic factors related to MAFLD. We used a Korean population-based sample of 2282 subjects with MAFLD and a control group of 4669. We replicated the results in a validation sample which included 639 patients with MAFLD and 1578 controls. Additionally, we categorized participants into three groups, no MAFLD, metabolic dysfunction (MD)-MAFLD, and overweight/obese-MAFLD. After adjusting for age, sex, and principal component scores, rs738409 [risk allele G] and rs3810622 [risk allele T], located in the PNPLA3 gene, showed significant associations with MAFLD (P-values, discovery set = 1.60 × 10–15 and 4.84 × 10–10; odds ratios, 1.365 and 1.284, validation set = 1.39 × 10–4, and 7.15 × 10–4, odds ratios, 1.299 and 1.264, respectively). An additional SNP rs59148799 [risk allele G] located in the GATAD2A gene showed a significant association with MAFLD (P-values, discovery set = 2.08 × 10–8 and validation set = 0.034, odds ratios, 1.387 and 1.250). rs738409 was significantly associated with MAFLD subtypes ([overweight/obese-MAFLD; odds ratio (95% confidence interval), P-values, 1.515 (1.351–1.700), 1.43 × 10–12 and MD-MAFLD: 1.300 (1.191–1.416), 2.90 × 10–9]. There was a significant relationship between rs3810622 and overweight/obese-MAFLD and MD-MAFLD [odds ratios (95% confidence interval), P-values, 1.418 (1.258, 1.600), 1.21 × 10–8 and 1.225 (1.122, 1.340), 7.06 × 10–6, respectively]; the statistical significance remained in the validation set. PNPLA3 was significantly associated with MAFLD and MAFLD subtypes in the Korean population. These results indicate that genetic factors play an important role in the pathogenesis of MAFLD. [ABSTRACT FROM AUTHOR]

Genome-wide association studies have identified several genetic variants associated with nonalcoholic fatty liver disease. To emphasize metabolic abnormalities in fatty liver, metabolic (dysfunction)-associated fatty liver disease (MAFLD) has been introduced; thus, we aimed to investigate single-nucleotide polymorphisms related to MAFLD and its subtypes. A genome-wide association study was performed to identify genetic factors related to MAFLD. We used a Korean population-based sample of 2282 subjects with MAFLD and a control group of 4669. We replicated the results in a validation sample which included 639 patients with MAFLD and 1578 controls. Additionally, we categorized participants into three groups, no MAFLD, metabolic dysfunction (MD)-MAFLD, and overweight/obese-MAFLD. After adjusting for age, sex, and principal component scores, rs738409 [risk allele G] and rs3810622 [risk allele T], located in the PNPLA3 gene, showed significant associations with MAFLD (P-values, discovery set = 1.60 × 10–15 and 4.84 × 10–10; odds ratios, 1.365 and 1.284, validation set = 1.39 × 10–4, and 7.15 × 10–4, odds ratios, 1.299 and 1.264, respectively). An additional SNP rs59148799 [risk allele G] located in the GATAD2A gene showed a significant association with MAFLD (P-values, discovery set = 2.08 × 10–8 and validation set = 0.034, odds ratios, 1.387 and 1.250). rs738409 was significantly associated with MAFLD subtypes ([overweight/obese-MAFLD; odds ratio (95% confidence interval), P-values, 1.515 (1.351–1.700), 1.43 × 10–12 and MD-MAFLD: 1.300 (1.191–1.416), 2.90 × 10–9]. There was a significant relationship between rs3810622 and overweight/obese-MAFLD and MD-MAFLD [odds ratios (95% confidence interval), P-values, 1.418 (1.258, 1.600), 1.21 × 10–8 and 1.225 (1.122, 1.340), 7.06 × 10–6, respectively]; the statistical significance remained in the validation set. PNPLA3 was significantly associated with MAFLD and MAFLD subtypes in the Korean population. These results indicate that genetic factors play an important role in the pathogenesis of MAFLD. [ABSTRACT FROM AUTHOR]

Objective To investigate the influence of metabolic associated fatty liver disease (MAFLD) on carotid stenosis. Methods This study was conducted among the patients who underwent abdominal ultrasound and cervical vascular ultrasound at the same time during hospitalization in Department of Gastroenterology, The Second Affiliated Hospital of Kunming Medical University, from January 1, 2014 to June 30, 2020, and baseline data and clinical diagnosis were collected. According to medical history, clinical tests, and imaging indicators, they were divided into MAFLD group with 469 patients and non-MAFLD group with 365 patients. Carotid artery were assessed as normal carotid artery, carotid stenosis ＜50%, and carotid stenosis ≥50% according to the degree of stenosis. The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed quantitative data between two groups; the chi-square test was used for comparison of qualitative data between two groups. The univariate and multivariate logistic regression analyses were used to investigate the influencing factors carotid stenosis. Results Compared with the non-MAFLD group, the MAFLD group had a significantly higher proportion of patients with carotid stenosis ≥50% (10.66% vs 5.21%, χ~2=8.050, P=0.005). The univariate logistic regression analysis showed that there were significant differences between the two groups in the proportion of male patients, smoking, MAFLD, body mass index (BMI), total cholesterol, high-density lipoprotein (HDL), administration of lipid-lowering drugs, systolic pressure, hypertension or medication, type 2 diabetes, insulin resistance, and aspartate aminotransferase (AST). After adjustment for sex, smoking, HDL, BMI, history of hypertension or medication, type 2 diabetes, and AST, the multivariate logistic regression analysis showed that MAFLD was a risk factor for carotid stenosis (≥50%) (odds ratio=1.979, 95% confidence interval: 1.055-3.713, P=0.033). Conclusion MAFLD is an independent risk factor for carotid stenosis (≥50%). [ABSTRACT FROM AUTHOR]

Oxidative stress is one of the pillars crucial in the development of a non-alcoholic fatty liver disease (NAFLD) and may cause DNA damage. Since the main pathway responsible for the repair of oxidative DNA damage is the base-excision repair (BER) pathway, we examined the relationship between the presence of different genetic variants of BER-associated genes and the risk of NAFLD. The study evaluates seven single nucleotide polymorphisms (SNPs) within five genes, hOGG1, APEX1, NEIL1, LIG3, LIG1, in 150 NAFLD patients and 340 healthy controls. The genotyping was performed using TaqMan probes and the results were presented as odds ratio with its corresponding 95% confidence interval. The following SNPs were assessed in the study: hOGG1 (rs1052133), APEX1 (rs176094 and rs1130409), NEIL1 (rs4462560), LIG3 (rs1052536), LIG3 (rs4796030), and LIG1 (rs20579). Four of the investigated SNPs, i.e., rs176094, rs1130409, rs4462560 and rs4796030, were found to be associated with NAFLD risk. Furthermore, the occurrence of insulin resistance in patients with steatosis depended on various LIG3 genetic variants. The findings imply the impact of genes involved in BER on NAFLD and fatty liver-related insulin sensitivity. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease( NAFLD) has become the most important chronic liver disease in the world, but there is still no approved drug for clinical practice. Due to the heterogeneity of NAFLD itself, although drug therapy is being developed, the response rate seems to remain low. In order to meet the needs of clinical trial design and provide accurate information for drug developers, relevant scholars have proposed to change the name of NAFLD to metabolic associated fatty liver disease This article summarizes the origin of NAFLD heterogeneity and the background of NAFLD renaming, so as to provide new ideas for accelerating the development of new therapies. [ABSTRACT FROM AUTHOR]