(Download) "Newly Identified Apolipoprotein AV Gene Predisposes to High Plasma Triglycerides in Familial Combined Hyperlipidemia (Technical Briefs)" by Clinical Chemistry ~ eBook PDF Kindle ePub Free
eBook details
- Title: Newly Identified Apolipoprotein AV Gene Predisposes to High Plasma Triglycerides in Familial Combined Hyperlipidemia (Technical Briefs)
- Author : Clinical Chemistry
- Release Date : January 01, 2002
- Genre: Chemistry,Books,Science & Nature,
- Pages : * pages
- Size : 195 KB
Description
Familial combined hyperlipidemia (FCHL) is the commonest form of hereditary hyperlipidemia (1,2). Its primary defect is increased secretion of hepatic triglyceride (TG)-rich apolipoprotein B (apo B)-containing particles (VLDL) (3) and impaired clearance of postprandial lipoproteins (4), which increases the number of circulating TG-rich lipoproteins. FCHL is present in up to 20% of survivors of myocardial infarction, and it is considered a significant genetic risk factor for developing cardiovascular disease (1,5). The underlying genetic defect is unknown, although the disease has been linked to chromosomes 1 (6) and 11 (7). With regard to the latter, linkage has been identified in the AI-CIII-AIV cluster, encoded in chromosome 11823-q24, which has been repeatedly associated with FCHL as a site involved in modulating expression of the disease (8,9). This is in part explained by the role of apo C-III as a negative regulator of TG hydrolysis. Despite considerable effort, no functional variant has been detected that explains such modulatory action, and the search has been extended to the surrounding regions. In this context, the newly identified apo AV gene (APOAV) (10,11), adjacent to the AI-CIII-AIV gene cluster and with a clear impact on TG metabolism in animals (10), becomes a candidate. Association of this gene with plasma TG concentrations has also been reported in humans (10). We have explored such an association in FCHL. According to the nomenclature and methodology used by Pennacchio et al. (10), single-nucleotide polymorphism C/T number 3 (SNP3;1 is the common allele, 2 is the rare allele) was used as the genetic marker. Genotyping was performed with primers AV-1 (5'-GATTGATTCAAGAT-GCATTTAGGAC-3') and AV-2 (5'-000CAGGAACTGGAGCGAAATT-3'), which forced a MseI (New England Biolabs) site for enzymatic restriction. Associations were analyzed between the APOAV gene and TG metabolism in a population-based Spanish control group (12) (ESP controls; n = 408), a normolipidemic control group from The Netherlands (13) (NL controls; n = 89), and 16 FCHL families (9) (n = 103) with 42 hyperlipidemic and 61 normolipidemic first-degree relatives. Normolipidemic controls were selected on the basis of fasting normolipidemia (fasting plasma cholesterol and/or TGs below the 90th percentile) and normoglycemia with negative family history of diabetes, hyperlipidemia, and premature atherosclerosis. In the FCHL families, all index individuals were on lipid-lowering diets and were free of medication for a period of at least 2 months before blood sampling. At inclusion in the study, hyperlipidemic relatives were identified on the basis of the one lipid measurement if they presented with plasma cholesterol concentrations [greater than or equal to] 6.4 mmol/L and/or plasma TGs [greater than or equal to] 2.8 mmol/L or increased above the 95th percentile for age and gender in the case of offspring below the age of 19 years. Relatives who did not meet these criteria were assigned the normolipidemic status. All individuals recruited into the study gave fully informed written consent, and the protocol was approved by the local Ethical Committees.
 "Newly Identified Apolipoprotein AV Gene Predisposes to High Plasma Triglycerides in Familial Combined Hyperlipidemia (Technical Briefs)" by Clinical Chemistry ~ eBook PDF Kindle ePub Free){kind=link}