RESUMO
Several genome scans in search of high-density lipoprotein (HDL) quantitative trait loci (QTLs) have been performed. However, to date the actual identification of genes implicated in the regulation of common forms of HDL abnormalities remains unsuccessful. This may be due, in part, to the oligogenic and multivariate nature of HDL regulation, and potentially, pleiotropy affecting HDL and other lipid-related traits. Using a Bayesian Markov Chain Monte Carlo (MCMC) approach, we recently provided evidence of linkage of HDL level variation to the APOA1-C3-A4-A5 gene complex, in familial combined hyperlipidemia pedigrees, with an estimated number of two to three large QTLs remaining to be identified. We also presented results consistent with pleiotropy affecting HDL and triglycerides at the APOA1-C3-A4-A5 gene complex. Here we use the same MCMC analytic strategy, which allows for oligogenic trait models, as well as simultaneous incorporation of covariates, in the context of multipoint analysis. We now present results from a genome scan in search for the additional HDL QTLs in these pedigrees. We provide evidence of linkage for additional HDL QTLs on chromosomes 3p14 and 13q32, with results on chromosome 3 further supported by maximum parametric and variance component LOD scores of 3.0 and 2.6, respectively. Weaker evidence of linkage was also obtained for 7q32, 12q12, 14q31-32 and 16q23-24.
Assuntos
HDL-Colesterol/genética , Hiperlipidemia Familiar Combinada/genética , Locos de Características Quantitativas , Adolescente , Adulto , Idoso , Teorema de Bayes , Criança , HDL-Colesterol/sangue , Cromossomos Humanos Par 3 , Feminino , Ligação Genética , Humanos , Hiperlipidemia Familiar Combinada/sangue , Padrões de Herança , Masculino , Cadeias de Markov , Pessoa de Meia-Idade , Método de Monte Carlo , LinhagemRESUMO
BACKGROUND: Nicotinic acid is an effective treatment for dyslipidemia, but the content of over-the-counter niacin is not federally regulated. As a result, patients may use preparations of over-the-counter niacin that do not contain free nicotinic acid. OBJECTIVE: To characterize the types, costs, and free nicotinic acid content of over-the-counter niacin preparations and to review literature on the use of over-the-counter niacin for dyslipidemia. DATA SOURCES: Commonly used over-the-counter niacin preparations (500-mg tablets or capsules) from the 3 categories of immediate-release, sustained-release, and no-flush were purchased at health food stores and pharmacies and from Internet-based vitamin companies. Pertinent literature on the use of over-the-counter niacin was obtained by searching PubMed. MEASUREMENTS: For each preparation studied, the monthly cost of therapy (at 2000 mg/d) and the free nicotinic acid content (quantified by high-performance liquid chromatography) were reported. DATA SYNTHESIS: On average, immediate-release niacin preparations cost 7.10 dollars per month, sustained-release preparations cost 9.75 dollars per month, and no-flush preparations cost 21.70 dollars per month. The average content of free nicotinic acid was 520.4 mg for immediate-release niacin, 502.6 mg for sustained-release niacin, and 0 for no-flush niacin. CONCLUSIONS: No-flush preparations of over-the-counter niacin contain no free nicotinic acid and should not be used to treat dyslipidemia. Over-the-counter sustained-release niacin contains free nicotinic acid, but some brands are hepatotoxic. Immediate-release niacin contains free nicotinic acid and is the least expensive form of over-the-counter niacin.