Phenotype expression in familial combined hyperlipidemia

Porkka, Kimmo; Nuotio, Ilpo; Pajukanta, Päivi; Ehnholm, Christian; Suurinkeroinen, Leena; Syvänne, Mikko; Lehtimäki, Terho; Lahdenkari, Anne-Tiina; Lahdenperä, Sanni; Ylitalo, Kati; Antikainen, Marjatta; Perola, Markus; Raitakari, Olli T.; Kovanen, Petri T.; Viikari, Jorma; Peltonen, Leena; Taskinen, Marja‐Riitta

doi:10.1016/s0021-9150(97)00134-2

Cited by 56 publications

(61 citation statements)

References 31 publications

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“…Therefore, researchers have stated that lipid levels are not the optimal phenotypical markers for elucidating the genetic background of FCHL (15). However, easily obtainable markers that directly reflect either the overproduction or clearance of lipid particles have not been available.…”

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confidence: 99%

Heritability and genetic loci of fatty liver in familial combined hyperlipidemia

Brouwers

Cantor

Kono

et al. 2006

Journal of Lipid Research

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VLDL overproduction, a process that is driven by an excess amount of hepatic fat, is a well-documented feature of familial combined hyperlipidemia (FCHL). The aims of this study were to investigate whether fatty liver, measured with ultrasound and as plasma alanine aminotransferase (ALT) levels, develops against a genetic background in FCHL and to identify chromosomal loci that are linked to these traits. In total, 157 FCHL family members and 20 spouses participated in this study. Radiological evidence of fatty liver was more prevalent not only in FCHL probands (40%) but also in their relatives (35%) compared with spouses (15%) (P , 0.05). Heritability calculations revealed that 20-36% of the variability in ALT levels could be attributed to genetic factors. Nonparametric quantitative trait locus (QTL) analysis revealed three significant (P , 0.001) loci with either the ultrasound or the ALT trait in the male sample: 1q42.3, 7p12-21, and 22p13-q11; none was found in the female sample or the entire group. Of these QTLs, the 7p region was consistent over time, because reanalysis with ALT levels that were determined during a visit 5 years earlier yielded similar results. This study shows that fatty liver is a heritable aspect of FCHL. Replication of particularly the 7p region is awaited.-Brouwers,

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confidence: 99%

Heritability and genetic loci of fatty liver in familial combined hyperlipidemia

Brouwers

Cantor

Kono

et al. 2006

Journal of Lipid Research

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“…[1][2][3] In a recent follow-up study, we showed that for the diagnosis FCH, only plasma TC and TG levels adjusted for age and gender are insufficient. 4 Furthermore, the FCH phenotype based on TC and/or TG levels alone is physiologically incoherent.…”

Section: Discussionmentioning

confidence: 99%

“…Not all research groups use the same criteria to establish the diagnosis of FCH. 2,3 There are even more fundamental problems. Among the most important is that the lipid phenotype can vary substantially within any individual.…”

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confidence: 99%

Nomogram to Diagnose Familial Combined Hyperlipidemia on the Basis of Results of a 5-Year Follow-Up Study

Veerkamp¹,

Graaf²,

Hendriks³

et al. 2004

Circulation

113

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Background-Familial combined hyperlipidemia (FCH) is traditionally diagnosed by total plasma cholesterol and/or triglyceride levels above the 90th percentile adjusted for age and gender. In a recent study, we showed that the diagnosis of FCH on the basis of these diagnostic criteria was inconsistent in 26% of the subjects over a 5-year period. This result emphasizes the need for reevaluation of the diagnostic criteria for FCH. Methods and Results-A total of 32 families (299 subjects) were studied in 1994 and 1999. A subject was defined "truly" FCH when diagnosed FCH in 1994 and/or 1999 on the basis of traditional plasma lipid criteria. Additional lipid and lipoprotein parameters, including apolipoprotein B (apoB) and small, dense LDL, were measured at both time points. In total, 121 subjects (40%) were defined as truly FCH. Multivariate analysis revealed that absolute apoB values combined with triglyceride and total cholesterol levels adjusted for age and gender best predicted truly FCH. A nomogram including these parameters is provided to simply and accurately calculate the probability to be affected by FCH. Furthermore, it is shown that when percentiles of triglyceride and total cholesterol adjusted for age and gender are not available in a population, the definition of FCH can be established on the basis of hypertriglyceridemia (Ͼ1.5 mmol/L) and hyper-apoB (Ͼ1200 mg/L). Conclusions-The diagnosis of FCH is best predicted by absolute apoB levels combined with triglyceride and total cholesterol levels adjusted for age and gender and can accurately be calculated by a nomogram. This definition is also a good predictor of cardiovascular risk in

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“…Familial combined hyperlipidemia is characterised by an overproduction of apo B and VLDL, often diminished HDL levels and small dense LDL particles. In children with FCHL, hyperlipidemia may not be evident until later in life (3,23). From a genetic point of view FCHL is complicated, involving many genes and gene-environment interactions (21).…”

Section: Discussionmentioning

confidence: 99%

Apolipoprotein B as a Marker of Familial Hyperlipoproteinemia

Sveger

Nordborg

2004

JAT

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Aims: Families with 10-12-year-old schoolchildren were informed about and asked to participate in a study to identify children with hyperlipoproteinemia. We hypothesised that children and families with familial blood lipid abnormalities, specifically those with familial hypercholesterolemia (FH) and familial combined hyperlipidemia (FCHL), could be identified by the child's apolipoprotein B level exceeding the 95th percentile. Methods: Written information and consent was distributed to the families. Families whose child had an apoB concentration exceeding the 95th percentile were further examined. Children and parents were divided into normal, high and very high low density lipoprotein cholesterol (LDLC) groups. In adults a high LDLC level was defined as

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Phenotype expression in familial combined hyperlipidemia

Cited by 56 publications

References 31 publications

Heritability and genetic loci of fatty liver in familial combined hyperlipidemia

Heritability and genetic loci of fatty liver in familial combined hyperlipidemia

Nomogram to Diagnose Familial Combined Hyperlipidemia on the Basis of Results of a 5-Year Follow-Up Study

Apolipoprotein B as a Marker of Familial Hyperlipoproteinemia

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