Mitochondrial haplogroup G is associated with nonalcoholic fatty liver disease, while haplogroup A mitigates the effects of PNPLA3

Gusdon, Aaron M.; You, Haisheng; Chen, Jing; Mathews, Clayton E.; Qu, Shen

doi:10.1002/edm2.187

Cited by 4 publications

(1 citation statement)

References 57 publications

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“…Mitochondrial haplotype plays an important role in the phenotypic expression of diseases. Mitochondrial haplogroup G is associated with nonalcoholic fatty liver disease ( Gusdonet al, 2021 ). The specific mtDNA background B5a1 was significantly associated with Southeast Asian G11778A LHON and appeared to modify the risk of visual loss ( Kaewsutthi et al, 2011 ).…”

Section: Disccusionmentioning

confidence: 99%

The Mitochondrial tRNAPhe 625G>A Mutation in Three Han Chinese Families With Cholecystolithiasis

Hou

et al. 2022

Front. Genet.

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In this study, we assessed three Chinese families with inherited cholecystolithiasis and conducted the clinical, genetic, and molecular characterization of these subjects. Eight of eighteen matrilineal relatives had a clinical phenotype in these three families. Sequence analysis of complete mitochondrial genomes in these probands identified the homoplasmic tRNAPhe 625 G > A mutation and distinct sets of mtDNA polymorphisms belonging to haplogroups H2, F4b, and M10a. The 625G > A mutation disturbed the classic G-C base-pairings at a highly conserved position 49 in the T-stem of mitochondrial tRNAs. Molecular dynamics simulation showed that the structure of tRNAphe with 625 G > A mutation was noticeably remodeled while compared with the isoform of the wild type. The occurrence of tRNAPhe 625 G > A mutation in these various genetically unrelated subjects strongly indicates that this mutation is involved in the pathogenesis of cholecystolithiasis. This is the first evidence that tRNA mutations are associated with cholecystolithiasis, and it provided more insights into the genetic mechanism of cholecystolithiasis.

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Section: Disccusionmentioning

confidence: 99%

The Mitochondrial tRNAPhe 625G>A Mutation in Three Han Chinese Families With Cholecystolithiasis

Hou

et al. 2022

Front. Genet.

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Association between mtDNA haplogroups and skeletal fluorosis in Han population residing in drinking water endemic fluorosis area of northern China

Ji,

Guo,

et al. 2023

International Journal of Environmental Health Research

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PNPLA3 I148M Interacts With Environmental Triggers to Cause Human Disease

Speliotes,

Schneider

2024

Liver International

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BackgroundMetabolic dysfunction‐associated steatotic liver disease (MASLD) affects up to 30% of Western populations. While obesity is a recognized risk factor, MASLD does not develop in all obese individuals, highlighting the need to understand genetic and environmental interactions. The PNPLA3 I148M variant has been identified as a key genetic risk factor, significantly increasing the likelihood of MASLD development and progression.MethodsWe reviewed current literature on the role of PNPLA3 I148M in MASLD, focusing on gene‐environment interactions involving diet, physical activity, obesity, and insulin resistance. We included studies analysing ethnic differences in PNPLA3 I148M prevalence and its association with MASLD. Additionally, we reviewed data on how PNPLA3 I148M influences the response to therapies, including lipid‐lowering medications and GLP‐1 agonists.ResultsThe PNPLA3 I148M variant markedly heightens MASLD risk, particularly in Hispanic populations, where a higher prevalence of MASLD is observed. Lifestyle factors such as high sugar intake, alcohol consumption, and physical inactivity exacerbate MASLD risk among I148M carriers. Evidence shows that insulin resistance amplifies MASLD risk associated with the I148M variant, especially in non‐diabetic individuals. Moreover, the PNPLA3 I148M variant interacts with other genetic loci, further modifying MASLD risk and disease course. The variant also influences treatment response, with variability observed in effectiveness of lipid‐lowering therapies and GLP‐1 agonists among carriers.ConclusionThe interplay between PNPLA3 I148M and environmental factors underscores the need for personalized MASLD prevention and treatment strategies. Targeting both genetic and lifestyle contributors may enhance MASLD management, offering a tailored approach to reducing disease burden.

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Mitochondrial haplogroup G is associated with nonalcoholic fatty liver disease, while haplogroup A mitigates the effects of PNPLA3

Cited by 4 publications

References 57 publications

The Mitochondrial tRNAPhe 625G>A Mutation in Three Han Chinese Families With Cholecystolithiasis

The Mitochondrial tRNAPhe 625G>A Mutation in Three Han Chinese Families With Cholecystolithiasis

Association between mtDNA haplogroups and skeletal fluorosis in Han population residing in drinking water endemic fluorosis area of northern China

PNPLA3 I148M Interacts With Environmental Triggers to Cause Human Disease

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