Molekulargenetische Diagnostik
Praxis Dr. Mato Nagel

Hyperalphalipoproteinämie 1

Hyperalphalipoproteinämie 1 ist eine Hyperlipoproteinämie, die allein durch hohe HDL-Spiegel gekennzeichnet ist und durch Mutationen im CETP-Gen verusrsacht wird. Der Vererbungsmodus ist unterschiedlich. Es sind dominante als auch rezessive Formen beschrieben. Meist zeichnen sich die Merkmalsträger durch eine besondere Langlebigkeit aus.

Klinischer Befund

Klinisch sind die Hyperalphalipoproteinämien durch ein eher erniedrigtes Risiko für Herz-Kreislauf-Erkrankungeen gekennzeichnet. Bei der Hyperalphalipoproteinämie 1 bestehen neben den hohen HDL auch besonders niedrige LDL-Werte, was die anti-atherogene Wirkung noch weiter verstärkt. Merkmalsträger erreichen oft ein beträchtliches Alter.

Diagnosestellung

Bei der Lipidelektrophorese fällt der besonders hohe alpha Peak auf. Die HDL-Partikel sind sowohl vermehrt als auch vergrößert. Gleichzeitig kommt es zu einer erniedrigung der LDL-Partikel.

Gliederung

Dyslipidämie
Apolipoprotein-Mangel
Betalipoprotein-Mangel
Epigenetische Dyslipidämie
Hyperalphalipoproteinämie 1
CETP
Hyperalphalipoproteinämie 2
Hyperlipämie
Hypoalphalipoproteinämie
Hypobetalipoproteinemie

Referenzen:

1.

Teslovich TM et. al. (2010) Biological, clinical and population relevance of 95 loci for blood lipids.

[^]
2.

Spirin V et al. (2007) Common single-nucleotide polymorphisms act in concert to affect plasma levels of high-density lipoprotein cholesterol.

[^]
3.

Inazu A et al. (1990) Increased high-density lipoprotein levels caused by a common cholesteryl-ester transfer protein gene mutation.

[^]
4.

Saito F et al. (1984) A pedigree of homozygous familial hyperalphalipoproteinemia.

[^]
5.

Kuivenhoven JA et al. (1998) The role of a common variant of the cholesteryl ester transfer protein gene in the progression of coronary atherosclerosis. The Regression Growth Evaluation Statin Study Group.

[^]
6.

Kathiresan S et. al. (2008) Polymorphisms associated with cholesterol and risk of cardiovascular events.

[^]
7.

Aulchenko YS et. al. (2009) Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts.

[^]
8.

Altshuler D et al. (1998) Genetic polymorphisms and disease.

[^]
9.

Durlach A et al. (1999) Sex-dependent association of a genetic polymorphism of cholesteryl ester transfer protein with high-density lipoprotein cholesterol and macrovascular pathology in type II diabetic patients.

[^]
10.

Schaefer EJ et al. (2000) Perspectives: Benefits of reducing low-density lipoprotein cholesterol concentrations to <100 mg/dL.

[^]
11.

Kronenberg F et al. (2002) Segregation analysis of HDL cholesterol in the NHLBI Family Heart Study and in Utah pedigrees.

[^]
12.

Klerkx AH et al. (2003) Haplotype analysis of the CETP gene: not TaqIB, but the closely linked -629C-->A polymorphism and a novel promoter variant are independently associated with CETP concentration.

[^]
13.

Brousseau ME et al. (2004) Effects of an inhibitor of cholesteryl ester transfer protein on HDL cholesterol.

[^]
14.

Borggreve SE et al. (2005) The effect of cholesteryl ester transfer protein -629C->A promoter polymorphism on high-density lipoprotein cholesterol is dependent on serum triglycerides.

[^]
15.

Mohrschladt MF et al. (2005) TaqIB polymorphism in CETP gene: the influence on incidence of cardiovascular disease in statin-treated patients with familial hypercholesterolemia.

[^]
16.

Frisdal E et al. (2005) Functional interaction between -629C/A, -971G/A and -1337C/T polymorphisms in the CETP gene is a major determinant of promoter activity and plasma CETP concentration in the REGRESS Study.

[^]
17.

Glueck CJ et al. (1975) Familial hyperalphalipoproteinemia.

[^]
18.

Glueck CJ et al. (1975) Familial hyper-alpha-lipoproteinemia: studies in eighteen kindreds.

[^]
19.

Glueck CJ et al. (1977) Neonatal familial hyperalphalipoproteinemia.

[^]
20.

Kondo I et al. (1989) DNA polymorphism at the locus for human cholesteryl ester transfer protein (CETP) is associated with high density lipoprotein cholesterol and apolipoprotein levels.

[^]
21.

Paigen B et al. (1987) Ath-1, a gene determining atherosclerosis susceptibility and high density lipoprotein levels in mice.

[^]
22.

Kurasawa T et al. (1985) Rate of cholesteryl ester transfer between high and low density lipoproteins in human serum and a case with decreased transfer rate in association with hyperalphalipoproteinemia.

[^]
23.

Koizumi J et al. (1985) Deficiency of serum cholesteryl-ester transfer activity in patients with familial hyperalphalipoproteinaemia.

[^]
24.

Siervogel RM et al. (1980) Familial hyper-alpha-lipoproteinemia in 26 kindreds.

[^]
25.

Fumeron F et al. (1995) Alcohol intake modulates the effect of a polymorphism of the cholesteryl ester transfer protein gene on plasma high density lipoprotein and the risk of myocardial infarction.

[^]
26.

Hannuksela ML et al. (1994) Relation of polymorphisms in the cholesteryl ester transfer protein gene to transfer protein activity and plasma lipoprotein levels in alcohol drinkers.

[^]
27.

Freeman DJ et al. (1994) Regulation of plasma HDL cholesterol and subfraction distribution by genetic and environmental factors. Associations between the TaqI B RFLP in the CETP gene and smoking and obesity.

[^]
28.

Zhong S et al. (1996) Increased coronary heart disease in Japanese-American men with mutation in the cholesteryl ester transfer protein gene despite increased HDL levels.

[^]
29.

Kuivenhoven JA et al. (1997) Heterogeneity at the CETP gene locus. Influence on plasma CETP concentrations and HDL cholesterol levels.

[^]
30.

Dullaart RP et al. (1997) Cholesteryl ester transfer protein gene polymorphism is a determinant of HDL cholesterol and of the lipoprotein response to a lipid-lowering diet in type 1 diabetes.

[^]