Heritability and genetic loci of fatty liver in familial combined hyperlipidemia

Brouwers, Martijn C.G.J.; Cantor, Rita M.; Kono, Naoko; Yoon, Jeong lim; Kallen, Carla J.H. van der; Bilderbeek-Beckers, Monique A.L.; Greevenbroek, Marleen M.J. van; Lusis, Aldons J.; Bruin, T.W.A. de

doi:10.1194/jlr.m600312-jlr200

Cited by 58 publications

(65 citation statements)

References 43 publications

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“…LDL-cholesterol was calculated using the Friedewald formula [13]. NEFA were assessed in EDTA plasma using an enzymatic colorimetric method (NEFA-C; Wako Chemicals, Neuss, Germany) [14]. Blood pressure was measured using an oscillometric precision blood pressure instrument (Maxi-Stabol 3; Speidel & Keller, now Welch Allyn, Skaneateles Falls, NY, USA) [15].…”

Section: Methodsmentioning

confidence: 99%

Discriminatory ability of simple OGTT-based beta cell function indices for prediction of prediabetes and type 2 diabetes: the CODAM study

et al. 2016

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Aims/hypothesis The hyperglycaemic clamp technique and the frequently sampled IVGTT are unsuitable techniques to assess beta cell function (BCF) in large cohorts. Therefore, the aim of this study was to evaluate the discriminatory ability of simple OGTT-based BCF indices for prediction of prediabetes (meaning impaired fasting glucose and/or impaired glucose tolerance) and type 2 diabetes. Methods Glucose metabolism status was assessed by 2 h 75 g OGTT at baseline (n = 476, mean age 59.2 years, 38.7% women) and after 7 years of follow-up (n = 416) in the Cohort on Diabetes and Atherosclerosis Maastricht (CODAM) study (1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009). Baseline plasma glucose, insulin and Cpeptide values during OGTTs were used to calculate 21 simple indices of BCF. Disposition indices (BCF index × Matsuda index), to compensate for the prevailing level of insulin resistance, were calculated for the BCF indices with the best discriminatory abilities. The discriminatory ability of the BCF indices was estimated by the area under the receiver operating characteristics curve (ROC AUC) with an outcome of incident prediabetes (n = 73) or type 2 diabetes (n = 60 and n = 18 cases, respectively, in individuals who were nondiabetic or had normal glucose metabolism at baseline). Results For incident prediabetes (n = 73), all ROC AUCs were less than 70%, whereas for incident type 2 diabetes, I 30 /I 0 , CP 30 /CP 0 , ΔI 30 /ΔG 30 , ΔCP 30 /ΔG 30 (where I, CP and G are the plasma concentrations of insulin, C-peptide and glucose, respectively, at the times indicated), and corrected insulin response at 30 min had ROC AUCs over 70%. In at-baseline non-diabetic individuals, disposition indices ΔI 30 /ΔG 30 , ΔCP 30 /ΔG 30 and corrected insulin response at 30 min had ROC AUCs of over 80% for incident type 2 diabetes. Moreover, these BCF disposition indices had significantly better discriminatory abilities for incident type 2 diabetes than the Matsuda index alone. Conclusions/interpretation BCF indices reflecting earlyphase insulin secretion have the best ability to discriminate individuals who will develop prediabetes and type 2 diabetes. Of these, ΔCP 30 /ΔG 30 , often referred to as the Cpeptidogenic index, performed consistently well.

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Section: Methodsmentioning

confidence: 99%

Discriminatory ability of simple OGTT-based beta cell function indices for prediction of prediabetes and type 2 diabetes: the CODAM study

et al. 2016

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“…A family study of 157 individuals with familial combined hyperlipidemia showed that both the presence of fatty liver and the levels of alanine aminotransferase (ALT) were increased both in index dyslipidemic patients and in normolipidemic family members. 59 A case-control family aggregation study of 20 NAFLD patients showed that IR occurs more commonly within families of NAFLD patients, with significantly higher risks of T2DM…”

Section: Family Studiesmentioning

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

399

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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“…Brouwers et al used nonparametric quantitative trait locus analysis to identify three loci associated with fatty liver in males, as determined by serum alanine aminotransferase (ALT) activity and ultrasound in 157 members from Dutch familial combined hyperlipidemia kindred ( 48 ). Of the familial combined hyperlipidemia probands, 40% had fatty liver, compared with 35% of relatives and 15% of spouses.…”

Section: Impaired Hepatic Triglyceride Exportmentioning

confidence: 99%

Genetic determinants of hepatic steatosis in man

Hooper

Adams

Burnett

2011

Journal of Lipid Research

115

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in childhood in some individuals, with a prevalence of 10% found in an autopsy study of 2-19 year olds from the United States ( 5 ). The prevalence of NAFLD increases with advancing age, with a peak between 40 and 69 years of age ( 2, 6 ).A cut-off of 5.5% hepatic steatosis has been accepted as the threshold to diagnose fatty liver, based on the 95th centile of hepatic fat content in low-risk subjects [normal body mass index (BMI), normal glucose tolerance, lack of excessive alcohol ingestion, and normal liver function tests] ( 1, 7 ). Subjects with NAFLD may have a range of histopathological changes (

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Heritability and genetic loci of fatty liver in familial combined hyperlipidemia

Cited by 58 publications

References 43 publications

Discriminatory ability of simple OGTT-based beta cell function indices for prediction of prediabetes and type 2 diabetes: the CODAM study

Discriminatory ability of simple OGTT-based beta cell function indices for prediction of prediabetes and type 2 diabetes: the CODAM study

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

Genetic determinants of hepatic steatosis in man

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