The Kruppel-Like Factor 6 Genotype Is Associated With Fibrosis in Nonalcoholic Fatty Liver Disease

Miele, Luca; Beale, Gary; Patman, Gillian; Nobili, Valério; Leathart, Julian; Grieco, Antonio; Abate, M.L.; Friedman, Scott L.; Narla, Goutham; Bugianesi, Elisabetta; Day, Christopher P.; Reeves, Helen L.

doi:10.1053/j.gastro.2008.04.004

Cited by 175 publications

(124 citation statements)

References 32 publications

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“…Variant 1 of the rs3750861 functional polymorphism (KLF6-SV1) of this gene is associated with more advanced stages of hepatic fibrosis and is an independent predictor of NASH. 80 In the same region of NCAN the trans-membrane 6 superfamily member 2 (TM6SF) gene has been identified. TM6SF encodes for a trans-membrane protein, which seems to be involved in very-low density lipoprotein (VLDL) secretion; its malfunctioning predisposed to NAFLD in some studies.…”

Section: Molecular Geneticsmentioning

confidence: 99%

Epidemiological modifiers of non-alcoholic fatty liver disease: Focus on high-risk groups

Lonardo

Bellentani

Argo

et al. 2015

Digestive and Liver Disease

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403

318

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We aimed to illustrate the epidemiology of nonalcoholic fatty liver disease in high-risk groups, which were identified based on existing literature. To this end, PubMed was searched to retrieve original articles published through May 2015 using relevant and pertinent keywords "nonalcoholic fatty liver disease" and "diabetes", "obesity", "hyperlipidemia", "familial heterozygous hypobelipoproteinemia", "hypertension", "metabolic syndrome", "ethnicity", "family history" or "genetic polymorphisms".We found that age, sex and ethnicity are major physiologic modifiers of the risk of nonalcoholic fatty liver disease, along with belonging to "nonalcoholic fatty liver disease families" and carrying risk alleles for selected genetic polymorphisms. Metabolic syndrome, diabetes, obesity, mixed hyperlipidaemia and hypocholesterolemia due to familial hypobetalipoproteinaemia are the major metabolic modifiers of nonalcoholic fatty liver disease risk. Compared to these metabolic conditions, however, arterial hypertension appears to carry a relatively more modest risk of nonalcoholic fatty liver disease.A better understanding of the epidemiology of nonalcoholic fatty liver disease may result in a more liberal policy of case finding among high-risk groups.

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Section: Molecular Geneticsmentioning

confidence: 99%

Epidemiological modifiers of non-alcoholic fatty liver disease: Focus on high-risk groups

Lonardo

Bellentani

Argo

et al. 2015

Digestive and Liver Disease

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403

318

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“…The I148M variant influences liver fat without independently of body mass index, dyslipidemia, or insulin resistance, and it has been associated with severe steatosis, NASH, and liver fibrosis (Valenti et al 2002(Valenti et al , 2006(Valenti et al , 2010aMiele et al 2008;Dongiovanni et al 2010), even if severe obesity exposed an association between I148M, insulin resistance, and lower triglycerides in Northern European subjects (Krarup et al 2012;Palmer et al 2012). We previously showed that in overweight children with increased liver enzymes, the PNPLA3 I148M polymorphism is enriched compared to the general population (homozygosity for the 148M risk allele was 16 vs. 5 % in the general population) and represents a non-invasive early marker of NASH and fibrosis (Valenti et al 2010a).…”

Section: Introductionmentioning

confidence: 99%

Influence of dietary pattern, physical activity, and I148M PNPLA3 on steatosis severity in at-risk adolescents

Nobili

Liccardo

Bedogni³

et al. 2014

Genes Nutr

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Evidence relating dietary patterns to obesity and related disorders such as non-alcoholic fatty liver disease (NAFLD) is limited in pediatric age. Aim of this study was to analyze the association between dietary patterns, obesity and development of severe steatosis and the metabolic syndrome in a series of children and adolescents referred for suspected NAFLD, and the interaction with the rs738409 I148M PNPLA3 polymorphism. Two hundred patients (112 females) had completed a food frequency and demographic questionnaire. Nearly 58 % were obese, and 32 % were overweight. Mild, moderate, and severe fatty liver was present in 60 (30 %), 87 (44 %), and 51 (26 %) participants, respectively. A great proportion of overweight/obese children and adolescents reported a correct dietary pattern. At multivariate ordinal regression analysis considering demographic, anthropometric, genetic, and behavioral determinants, the major determinant of steatosis severity was PNPLA3 I148M genotype (p \ 0.0001), followed by older age (p = 0.017), higher waist circumference (p = 0.016), and less time spent practising physical exercise (p = 0.034). Furthermore, there was a significant interaction between PNPLA3 I148M and intake of sweetened beverages (p = 0.033) and of vegetables (p = 0.038).In conclusion, although dietary pattern was reportedly correct in at-risk overweight adolescents with NAFLD, we report a novel interaction between PNPLA3 I148M and dietary components with the severity of steatosis.

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“…SNPs have been found in genes encoding for: the manganese superoxide dismutase (SOD2) regulating mitochondrial import and anti-oxidant activity [18]; the transcription factor Kruppel-like factor 6 (KLF6) regulating metabolism in hepatocytes and fibro genesis in hepatic stellate cells [19]; and the lipin-1 regulating the flux of free fatty acids between the adipose tissue and the liver whose expression is deregulated during steatosis [22]. Finally, there is a growing awareness that phenotypic expression of some genetic variants may be age-related.…”

Section: Nalfd: the Liver At The Centermentioning

confidence: 99%

Nonalcoholic fatty liver disease as trigger of cardiovascular and metabolic complication in metabolic syndrome

et al. 2015

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The Kruppel-Like Factor 6 Genotype Is Associated With Fibrosis in Nonalcoholic Fatty Liver Disease

Cited by 175 publications

References 32 publications

Epidemiological modifiers of non-alcoholic fatty liver disease: Focus on high-risk groups

Epidemiological modifiers of non-alcoholic fatty liver disease: Focus on high-risk groups

Influence of dietary pattern, physical activity, and I148M PNPLA3 on steatosis severity in at-risk adolescents

Nonalcoholic fatty liver disease as trigger of cardiovascular and metabolic complication in metabolic syndrome

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