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Genetic variation in the hepatic lipase gene is associated with combined hyperlipidemia, plasma lipid concentrations, and lipid-lowering drug response.
Am Heart J. 2005 Dec; 150(6):1154-62.AH

Abstract

BACKGROUND

Combined hyperlipidemia (CHL) is a very frequent dyslipidemia, being lipid-lowering drugs often necessary in its management. Some genetic loci have been associated with CHL, and modulation of lipid-lowering treatment by genetic polymorphisms has been reported. We have investigated whether common polymorphisms in the hepatic lipase gene (LIPC) influence the baseline lipid concentration and the response to atorvastatin or bezafibrate in patients with CHL.

METHODS

Two genetic polymorphisms in LIPC (-514C-->T and +651A-->G) were determined by polymerase chain reaction and restriction analysis in 118 subjects of the ATOMIX (Atorvastatin in Mixed dyslipidemia) study who were randomized to treatment with either atorvastatin or bezafibrate and in 114 normolipidemic controls.

RESULTS

The -514T allele frequency was higher in the ATOMIX group (0.297) than in the control group (0.193) (P = .01). The -514T allele carriers in the control group showed higher high-density lipoprotein cholesterol (HDL-C) concentrations than the -514C homozygotes, 50.8 +/- 1.86 versus 45.9 +/- 1.40 mg/dL (P = .02). The +651G carriers in the ATOMIX group showed lower total cholesterol and low-density lipoprotein cholesterol than the +651A homozygotes, 274 +/- 3.72 and 181 +/- 3.50 mg/dL versus 289 +/- 4.0 and 194 +/- 3.76 mg/dL, respectively (P < .01). Homozygotes for the -514C allele on bezafibrate treatment had greater decrease in triglycerides and greater increase in HDL-C than -514T allele carriers after 12 months of bezafibrate treatment, -39.4% and +35.8% versus -25.5% and +20.4%, respectively (P = .080 and P = .007, respectively).

CONCLUSIONS

A higher frequency of the -514T allele of LIPC suggests a role of this locus in the pathogenesis of CHL. The -514T allele is associated with higher HDL-C concentration in normolipidemic population. The -514C-->T polymorphism modulates the lipid-lowering response to bezafibrate, with a better effect in homozygous CC subjects.

Authors+Show Affiliations

Laboratorio de Investigación Molecular, Hospital Universitario Miguel Servet, Zaragoza, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16338252

Citation

Cenarro, Ana, et al. "Genetic Variation in the Hepatic Lipase Gene Is Associated With Combined Hyperlipidemia, Plasma Lipid Concentrations, and Lipid-lowering Drug Response." American Heart Journal, vol. 150, no. 6, 2005, pp. 1154-62.
Cenarro A, Artieda M, Gonzalvo C, et al. Genetic variation in the hepatic lipase gene is associated with combined hyperlipidemia, plasma lipid concentrations, and lipid-lowering drug response. Am Heart J. 2005;150(6):1154-62.
Cenarro, A., Artieda, M., Gonzalvo, C., Meriño-Ibarra, E., Arístegui, R., Gañán, A., Díaz, C., Sol, J. M., Pocoví, M., & Civeira, F. (2005). Genetic variation in the hepatic lipase gene is associated with combined hyperlipidemia, plasma lipid concentrations, and lipid-lowering drug response. American Heart Journal, 150(6), 1154-62.
Cenarro A, et al. Genetic Variation in the Hepatic Lipase Gene Is Associated With Combined Hyperlipidemia, Plasma Lipid Concentrations, and Lipid-lowering Drug Response. Am Heart J. 2005;150(6):1154-62. PubMed PMID: 16338252.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genetic variation in the hepatic lipase gene is associated with combined hyperlipidemia, plasma lipid concentrations, and lipid-lowering drug response. AU - Cenarro,Ana, AU - Artieda,Marta, AU - Gonzalvo,Carmen, AU - Meriño-Ibarra,Erardo, AU - Arístegui,Rosa, AU - Gañán,Alberto, AU - Díaz,Cristina, AU - Sol,Josep María, AU - Pocoví,Miguel, AU - Civeira,Fernando, AU - ,, PY - 2004/03/04/received PY - 2005/02/07/accepted PY - 2005/12/13/pubmed PY - 2006/2/16/medline PY - 2005/12/13/entrez SP - 1154 EP - 62 JF - American heart journal JO - Am Heart J VL - 150 IS - 6 N2 - BACKGROUND: Combined hyperlipidemia (CHL) is a very frequent dyslipidemia, being lipid-lowering drugs often necessary in its management. Some genetic loci have been associated with CHL, and modulation of lipid-lowering treatment by genetic polymorphisms has been reported. We have investigated whether common polymorphisms in the hepatic lipase gene (LIPC) influence the baseline lipid concentration and the response to atorvastatin or bezafibrate in patients with CHL. METHODS: Two genetic polymorphisms in LIPC (-514C-->T and +651A-->G) were determined by polymerase chain reaction and restriction analysis in 118 subjects of the ATOMIX (Atorvastatin in Mixed dyslipidemia) study who were randomized to treatment with either atorvastatin or bezafibrate and in 114 normolipidemic controls. RESULTS: The -514T allele frequency was higher in the ATOMIX group (0.297) than in the control group (0.193) (P = .01). The -514T allele carriers in the control group showed higher high-density lipoprotein cholesterol (HDL-C) concentrations than the -514C homozygotes, 50.8 +/- 1.86 versus 45.9 +/- 1.40 mg/dL (P = .02). The +651G carriers in the ATOMIX group showed lower total cholesterol and low-density lipoprotein cholesterol than the +651A homozygotes, 274 +/- 3.72 and 181 +/- 3.50 mg/dL versus 289 +/- 4.0 and 194 +/- 3.76 mg/dL, respectively (P < .01). Homozygotes for the -514C allele on bezafibrate treatment had greater decrease in triglycerides and greater increase in HDL-C than -514T allele carriers after 12 months of bezafibrate treatment, -39.4% and +35.8% versus -25.5% and +20.4%, respectively (P = .080 and P = .007, respectively). CONCLUSIONS: A higher frequency of the -514T allele of LIPC suggests a role of this locus in the pathogenesis of CHL. The -514T allele is associated with higher HDL-C concentration in normolipidemic population. The -514C-->T polymorphism modulates the lipid-lowering response to bezafibrate, with a better effect in homozygous CC subjects. SN - 1097-6744 UR - https://www.unboundmedicine.com/medline/citation/16338252/Genetic_variation_in_the_hepatic_lipase_gene_is_associated_with_combined_hyperlipidemia_plasma_lipid_concentrations_and_lipid_lowering_drug_response_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0002-8703(05)00124-9 DB - PRIME DP - Unbound Medicine ER -