Association Between LYPLAL1 rs12137855 Polymorphism With Ultrasound-Defined Non-Alcoholic Fatty Liver Disease in a Chinese Han Population

Yuan, Chen; Lu, Linlin; An, Baiquan; Jin, Wenwen; Dong, Qi; Xin, Yongning; Xuan, Shi‐Ying

doi:10.5812/hepatmon.33155

Cited by 8 publications

(7 citation statements)

References 35 publications

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“… 29 , 30 Besides, there are several MAFLD-related SNPs in Europeans for which there has been no association in Chinese populations. 31 – 33 Along the same line, lower genetic prediction accuracies (between 1.6-4.9-fold lower) were observed in other ethnicities compared to Europeans. 8 Hence, increasing the representation of diverse populations and studying other ethnicities has recently become a research priority to enhance understanding of the human genetic architecture and its translational implications.…”

Section: Discussionsupporting

confidence: 53%

Associations of Hydroxysteroid 17-beta Dehydrogenase 13 Variants with Liver Histology in Chinese Patients with Metabolic-associated Fatty Liver Disease

Liu¹,

Eslam²,

Zheng³

et al. 2021

Journal of Clinical and Translational Hepatology

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Background and Aims In Europeans, variants in the hydroxysteroid 17-beta dehydrogenase 13 ( HSD17B13 ) gene impact liver histology in metabolic-associated fatty liver disease (MAFLD). The impact of these variants in ethnic Chinese is unknown. The aim of this study was to investigate the potential associations in Chinese patients. Methods In total, 427 Han Chinese with biopsy-confirmed MAFLD were enrolled. Two single nucleotide polymorphisms in HSD17B13 were genotyped: rs72613567 and rs6531975. Logistic regression was used to test the association between the single nucleotide polymorphisms and liver histology. Results In our cohort, the minor allele TA of the rs72613567 variant was related to an increased risk of fibrosis [odds ratio (OR): 2.93 (1.20–7.17), p =0.019 for the additive model; OR: 3.32 (1.39–7.91), p =0.007 for the recessive model], representing an inverse association as compared to the results from European cohorts. In contrast, we observed a protective effect on fibrosis for the minor A allele carriers of the HSD17B13 rs6531975 variant [OR: 0.48 (0.24–0.98), p =0.043 for the additive model; OR: 0.62 (0.40–0.94), p =0.025 for the dominant model]. HSD17B13 variants were only associated with fibrosis but no other histological features. Furthermore, HSD17B13 rs6531975 modulated the effect of PNPLA3 rs738409 on hepatic steatosis. Conclusions HSD17B13 rs72613567 is a risk variant for fibrosis in a Han Chinese MAFLD population but with a different direction for allelic association to that seen in Europeans. These data exemplify the need for studying diverse populations in genetic studies in order to fine map genome-wide association studies signals.

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Section: Discussionsupporting

confidence: 53%

Associations of Hydroxysteroid 17-beta Dehydrogenase 13 Variants with Liver Histology in Chinese Patients with Metabolic-associated Fatty Liver Disease

Liu¹,

Eslam²,

Zheng³

et al. 2021

Journal of Clinical and Translational Hepatology

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“…Speliotes , Fox et al 2012, Randall et al 2013, Leon-Mimila et al 2015, Yuan et al 2015, Wang et al 2016, Chu et al 2017, we hypothesized that the female KO mice on HFHS diet may have elevated serum and liver triglycerides and increased liver damage as reflected by increased serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) or alkaline phosphatase (ALP). To determine whether disruption of Lyplal1 affected serum lipids or serum liver enzymes, we assayed serum from non-fasted mice on both chow and HFHS diets.…”

Section: Journal Of Molecular Endocrinologymentioning

confidence: 99%

Knockout of murine Lyplal1 confers sex-specific protection against diet-induced obesity

Vohnoutka

Kuppa

Hegde

et al. 2023

Journal of Molecular Endocrinology

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Human genome-wide association studies found single nucleotide polymorphisms (SNPs) near LYPLAL1 (Lysophospholipase 1) that have sex-specific effects on fat distribution and metabolic traits. To determine whether altering LYPLAL1 affects obesity and metabolic disease we created and characterized a mouse knockout of Lyplal1. We fed the experimental group of mice high fat, high sucrose (HFHS) diet for 23 weeks, and the controls were fed regular chow diet. Here we show that CRISPR-Cas9 whole-body Lyplal1 knockout (KO) mice fed a HFHS diet showed sex-specific differences in weight gain and fat accumulation as compared to chow diet. Female, not male, KO mice weighed less than WT mice, had reduced body fat percentage, white fat mass, and adipocyte diameter not accounted for by changes in metabolic rate. Female, but not male, KO mice had increased serum triglycerides, decreased aspartate, and alanine aminotransferase. Lyplal1 KO mice of both sexes have reduced liver triglycerides and steatosis. These diet-specific effects resemble the effects of SNPs near LYPLAL1 in humans, suggesting that LYPLAL1 has an evolutionary conserved sex-specific effect on adiposity. This murine model can be used to study this novel gene-by-sex-by-diet interaction to elucidate the metabolic effects of LYPLAL1 on human obesity.

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“…Due to the reduced accumulation of fat storage in adipose depots of female Lyplal1 KO mice on a hypercaloric diet (HFHS diet; Figure 2) and association of SNPs near the Lyplal1 gene in humans with NAFLD, central adiposity/distribution of fat, and fasting serum triglyceride levels [7][8][9][10][11][12][13][14]16,37 , we hypothesized that the female KO mice on HFHS diet may have elevated serum and liver triglycerides and increased liver damage as reflected by increased serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), or alkaline phosphatase (ALP). To determine whether disruption of Lyplal1 affected serum lipids or serum liver enzymes we assayed serum from fasted and non-fasted mice on both chow and HFHS diets.…”

Section: Lyplal1 Ko Mice Have Reduced Liver Steatosis Compared To Wt Littermatesmentioning

confidence: 99%

Knockout of murine Lyplal1 confers sex-specific protection against diet-induced obesity

Vohnoutka

Kuppa

Hegde

et al. 2021

Preprint

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Human genome-wide association studies found SNPs near LYPLAL1 that have sex-specific effects on fat distribution and metabolic traits. To determine whether altering LYPLAL1 affects obesity and metabolic disease we created and characterized a mouse knockout of Lyplal1. Here we show that CRISPR-Cas9 whole-body Lyplal1 knockout (KO) mice fed a high fat, high sucrose (HFHS) diet showed sex-specific differences in weight gain and fat accumulation. Female, not male, KO mice weighed less than WT mice, had reduced body fat percentage, white fat mass, and adipocyte diameter not accounted for by changes in metabolic rate. Female, but not male, KO mice had increased serum triglycerides, decreased aspartate, and alanine aminotransferase. Lyplal1 KO mice of both sexes have reduced liver triglycerides and steatosis. These diet-specific effects resemble the effects of SNPs near LYPLAL1 in humans, suggesting that LYPLAL1 has an evolutionary conserved sex-specific effect on adiposity. This murine model can be used to study this novel gene-by-sex-by-diet interaction to elucidate the metabolic effects of LYPLAL1 on human obesity.

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Association Between LYPLAL1 rs12137855 Polymorphism With Ultrasound-Defined Non-Alcoholic Fatty Liver Disease in a Chinese Han Population

Cited by 8 publications

References 35 publications

Associations of Hydroxysteroid 17-beta Dehydrogenase 13 Variants with Liver Histology in Chinese Patients with Metabolic-associated Fatty Liver Disease

Associations of Hydroxysteroid 17-beta Dehydrogenase 13 Variants with Liver Histology in Chinese Patients with Metabolic-associated Fatty Liver Disease

Knockout of murine Lyplal1 confers sex-specific protection against diet-induced obesity

Knockout of murine Lyplal1 confers sex-specific protection against diet-induced obesity

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