Article

Haplotype analyses of the APOA5 gene in patients with familial combined hyperlipidemia.

Department of Medicine, Division of General Internal Medicine, 463, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
Biochimica et Biophysica Acta (Impact Factor: 4.66). 01/2007; 1772(1):81-8. DOI: 10.1016/j.bbadis.2006.10.012
Source: PubMed

ABSTRACT Familial combined hyperlipidemia (FCH) is the most common genetic lipid disorder with an undefined genetic etiology. Apolipoprotein A5 gene (APOA5) variants were previously shown to contribute to FCH. The aim of the present study was to evaluate the association of APOA5 variants with FCH and its related phenotypes in Dutch FCH patients. Furthermore, the effects of variants in the APOA5 gene on carotid intima-media thickness (IMT) and cardiovascular disease (CVD) were examined.
The study population consisted of 36 Dutch families, including 157 FCH patients. Two polymorphisms in the APOA5 gene (-1131T>C and S19W) were genotyped.
Haplotype analysis of APOA5 showed an association with FCH (p=0.029), total cholesterol (p=0.031), triglycerides (p<0.001), apolipoprotein B (p=0.011), HDL-cholesterol (p=0.013), small dense LDL (p=0.010) and remnant-like particle cholesterol (p=0.001). Compared to S19 homozygotes, 19W carriers had an increased risk of FCH (OR=1.6 [1.0-2.6]; p=0.026) and a more atherogenic lipid profile, reflected by higher triglyceride (+22%) and apolipoprotein B levels (+5%), decreased HDL-cholesterol levels (-7%) and an increased prevalence of small dense LDL (16% vs. 26%). In carriers of the -1131C allele, small dense LDL was more prevalent than in -1131T homozygotes (29% vs. 16%). No association of the APOA5 gene with IMT and CVD was evident.
In Dutch FCH families, variants in the APOA5 gene are associated with FCH and an atherogenic lipid profile.

0 Bookmarks
 · 
76 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Although low-density lipoprotein cholesterol (LDL-C) is the main lipid target for cardiovascular risk reduction, recent studies suggest that other lipid indicies are also associated with vascular events. We hypothesized that the association of triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C) with atherosclerotic stroke (AS) differs depending on LDL-C levels. Data prospectively collected on subjects admitted with acute ischemic stroke to a university medical center were analyzed. We divided the patients into AS and non-atherosclerotic stroke (NAS) groups and independent association of lipid parameters and genetic influences of apolipoprotein A5 (ApoA5) polymorphisms with AS were evaluated. Of 268 patients, 160 (59.7%) were classified with AS and 108 (40.3%) were classified with NAS. Vascular risk factors were more prevalent in AS patients than in those with NAS; additionally, AS patients' anthropometric indexes and laboratory findings showed that they were prone to atherosclerosis. AS was independently associated with fasting TG (OR per 10 mg/dL increase, 1.38; 95% CI, 1.16-1.64; OR for highest vs. lowest tertile, 12.85; 95% CI, 3.31-49.85), HDL-C (OR per 10 mg/dL increase, 0.61; 95% CI, 0.42-0.88; OR for lowest vs. highest tertile, 4.28; 95% CI, 1.16-15.86), and nonfasting TG (OR per 10 10 mg/dL increase, 1.25; 95% CI, 1.11-1.42; OR for highest vs. lowest tertile, 8.20; 95% CI, 1.98-33.88) only among patients with LDL <100 mg/dL. No interaction was observed between fasting and nonfasting TG and ApoA5 polymorphisms. In conclusion, fasting and nonfasting TG and HDL-C were associated with AS only when patients had low levels of LDL-C. Non-LDL-C may have an additional role in addition to the LDL-C levels in AS development.
    Atherosclerosis 05/2012; 223(2):463-7. DOI:10.1016/j.atherosclerosis.2012.05.011 · 3.71 Impact Factor
  • Diabetologie und Stoffwechsel 06/2008; 3(3):153-158. DOI:10.1055/s-2008-1004769 · 0.31 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Les hypertriglycéridémies (HTG) génétiques sont en apparence peu fréquentes face à la multitude d’étiologies d’HTG secondaires et plus particulièrement à la fréquence des HTG associées au syndrome métabolique et au diabète de type 2. Néanmoins, cette impression de rareté est trompeuse, car l’hyperlipidémie combinée familiale (HCF) constitue l’une des plus communes maladies génétiques dans la population générale, avec une prévalence de 1 % chez les adultes. De plus, dans les formes apparemment secondaires, il existe fréquemment des anomalies génétiques sous-jacentes qui constituent un facteur essentiel d’accentuation. Le praticien est souvent déconcerté par la présentation polymorphe de ces dyslipidémies. Il doit savoir qu’un même génotype se traduira par une présentation phénotypique éminemment variable selon les cofacteurs environnementaux, les interactions médicamenteuses, et la modulation en parallèle par d’autres variants génétiques impliqués plus ou moins directement dans le métabolisme des lipoprotéines. Malgré 50 années de recherches, notre compréhension de la physiopathologie des HTG est encore imparfaite. Il reste certainement plusieurs gènes clés à identifier. Ainsi, la récente identification de l’apolipoprotéine (apo) AV a apporté un nouvel éclairage sur le mécanisme des hyperchylomicronémies. Cependant, 30 % de ces dernières restent actuellement inexpliquées.
    Médecine des Maladies Métaboliques 01/2008; 2(1). DOI:10.1016/S1957-2557(08)70004-X

Full-text (2 Sources)

Download
31 Downloads
Available from
May 21, 2014