Validation of genetic variants associated with metabolic dysfunction-associated fatty liver disease in an ethnic Chinese population

Lee, Guan Huei; Phyo, Wah Wah; Loo, Wai Mun; Kwok, Raymond; Ahmed, Tasnim; Shabbir, Asim; So, Jimmy Bok Yan; Koh, Calvin Jianyi; Hartono, Juanda Leo; Muthiah, Mark; Lim, Kieron; Tan, Poh Seng; Lee, Yin Mei; Lim, Seng Gee; Dan, Yock Young

doi:10.4254/wjh.v12.i12.1228

Cited by 10 publications

(5 citation statements)

References 35 publications

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“…Further, the authors if the related papers have tended to define MAFLD according to the diagnostic criteria for NAFLD. Lee et al 21 compared the association of genetic alleles such as NCAN, glucokinase regulator, LY-PLAL1, PNPLA3, PPP1R3B, FDFT1, COL13A1, EFCAB4B, PZP, and TM6SF2 between MAFLD patients and patients without hepatic steatosis in their Chinese cohort. They found that the PNPLA3 homozygous GG allele, higher BMI, and hypertriglyceridemia were independent predictors of MAFLD.…”

Section: Genetic Aspects Of Nafld and Mafldmentioning

confidence: 99%

Metabolic-associated Fatty Liver Disease (MAFLD): A Multi-systemic Disease Beyond the Liver

Kaya¹,

Yılmaz²

2021

J Clin Transl Hepatol

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Nonalcoholic fatty liver disease (NAFLD) is a multisystemic clinical condition that presents with a wide spectrum of extrahepatic manifestations, such as obesity, type 2 diabetes mellitus, metabolic syndrome, cardiovascular diseases, chronic kidney disease, extrahepatic malignancies, cognitive disorders, and polycystic ovarian syndrome. Among NAFLD patients, the most common mortality etiology is cardiovascular disorders, followed by extrahepatic malignancies, diabetes mellitus, and liver-related complications. Furthermore, the severity of extrahepatic diseases is parallel to the severity of NAFLD. In clinical practice, awareness of the associations of concomitant diseases is of major importance for initiating prompt and timely screening and multidisciplinary management of the disease spectrum. In 2020, a consensus from 22 countries redefined the disease as metabolic (dysfunction)-associated fatty liver disease (MAFLD), which resulted in the redefinition of the corresponding population. Although the patients diagnosed with MAFLD and NAFLD mostly overlap, the MAFLD and NAFLD populations are not identical. In this review, we compared the associations of key extrahepatic diseases between NAFLD and MAFLD.

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Section: Genetic Aspects Of Nafld and Mafldmentioning

confidence: 99%

Metabolic-associated Fatty Liver Disease (MAFLD): A Multi-systemic Disease Beyond the Liver

Kaya¹,

Yılmaz²

2021

J Clin Transl Hepatol

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“…Additionally, a recent study by Luukkonen et al 37 found two subtypes of NAFLD where the metabolic subtype of NAFLD was substantially more affected by insulin resistance compared to the genetic subtype of NAFLD. PNPLA3 mutations have been found to be prevalent amongst Asians affecting 13% to 19% 38 and may explain the ndings of the LCA analysis.…”

Section: Discussionmentioning

confidence: 93%

Factors Associated with Risk of NAFLD and Progression in Multiethnic Asians. A Latent Class and Machine Learning Analysis

Nah

Kaewdech

et al. 2022

Preprint

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Introduction Non-alcoholic fatty liver disease (NAFLD) is the commonest liver condition globally. However, Asians with NAFLD are significantly different from the west. Despite the significant prevalence of the disease, studies on Asians particularly from southeast Asians are lacking. Herein, we examine the prevalence, risk factors and different classes of NAFLD based on a multicenter cohort study from five centers in Asia. Methods A multicenter study involving the use of vibration-controlled transient elastography (VCTE) for the assessment of NAFLD based on a cutoff of ≥ 288 dB/m and liver fibrosis was examined through liver stiffness measures (LSM). Risk factors were examined through risk ratios (RR) from a generalized linear model and gradient boosting machines (GBM) machine learning model. A latent class analysis (LCA) was additionally conducted to explore subtypes of NAFLD in Asia. Results Of the 1,686 individuals included in the analysis, a total of 822 individuals were identified to have NAFLD. Factors that were associated with an increased risk of NAFLD included male gender, elevated serum lipid levels and diagnosis of hypertension or diabetes mellitus with similar findings from GBM. LCA identified two subtypes of NAFLD. Class 1 LCA had lower rates of metabolic dysfunction and were more likely lean relative to Class 2 LCA. However, both classes were at similar risk of clinically significant fibrosis and advance fibrosis. The risk of cirrhosis was higher in Class 1 LCA. Discussion The current analysis describes the prevalence and risk factors of NAFLD in a multiethnic Asian cohort with conventional regression and GBM analysis. Subclasses of NAFLD identified from LCA found that patients with lower rates of metabolic dysfunction had similar if not increased rates of fibrosis.

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“…On the other hand, GCKR rs1260326 and GCKR rs780094 were associated with increased TG levels and reduced serum fasting glucose, which was also found in some studies. 47 , 48 It was redundant with PNPLA3 rs738409 in the SNP–SNP interaction, as PNPLA3 rs738409 was associated with reduced serum TG concentration.…”

Section: Discussionmentioning

confidence: 99%

Genetic variants associated with metabolic dysfunction‐associated fatty liver disease in western China

Liao

et al. 2022

Clinical Laboratory Analysis

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Introduction We aimed to confirm the association between some single nucleotide polymorphisms (SNPs) and metabolic dysfunction‐associated fatty liver disease (MAFLD) in western China. Methods A total of 286 cases and 250 healthy controls were enrolled in our study. All samples were genotyped for patatin‐like phospholipase domain containing 3 ( PNPLA3 ) rs738409, transmembrane 6 superfamily member 2 ( TM6SF2 ) rs58542926, membrane‐bound O‐acyltransferase domain containing 7 ( MBOAT7 ) rs641738, glucokinase regulator ( GCKR ) rs1260326 and rs780094, and GATA zinc finger domain containing 2A ( GATAD2A ) rs4808199. Using logistic regression analysis, we evaluated the association between MAFLD and each SNP under different models. Multiple linear regression was used to find the association between SNPs and laboratory characteristics. Multifactor dimensionality reduction was applied to test SNP–SNP interactions. Results The recessive model and additive model of PNPLA3 rs738409 variant were related to MAFLD (odds ratio [OR] = 1.791 and 1.377, respectively, p = 0.038 and 0.027, respectively). However, after Benjamini‐Hochberg adjustment for multiple tests, all associations were no longer statistically significant. PNPLA3 rs738409 correlated with AST levels. GCKR rs780094 and rs1260326 negatively correlated with serum glucose but positively correlated with triglycerides in MAFLD. Based on MDR analysis, the best single‐locus and multilocus models for MAFLD risk were rs738409 and six‐locus models, respectively. Conclusions In the Han population in western China, no association was found between these SNPs and the risk of MAFLD. PNPLA3 rs738409 was associated with aspartate aminotransferase levels in MAFLD patients. GCKR variants were associated with increased triglyceride levels and reduced serum fasting glucose in patients with MAFLD.

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Validation of genetic variants associated with metabolic dysfunction-associated fatty liver disease in an ethnic Chinese population

Cited by 10 publications

References 35 publications

Metabolic-associated Fatty Liver Disease (MAFLD): A Multi-systemic Disease Beyond the Liver

Metabolic-associated Fatty Liver Disease (MAFLD): A Multi-systemic Disease Beyond the Liver

Factors Associated with Risk of NAFLD and Progression in Multiethnic Asians. A Latent Class and Machine Learning Analysis

Genetic variants associated with metabolic dysfunction‐associated fatty liver disease in western China

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