CLINICAL STUDY: ATHEROSCLEROSIS
Association between the –514 c t polymorphism of the hepatic lipase gene promoter and unstable carotid plaque in patients with severe carotid artery stenosis
Elisabetta Faggin, PhD*,
Alberto Zambon, MD, PhD ,
Massimo Puato, MD*,
Samir S. Deeb, PhD ,
Sandra Bertocco, MD,
Saverio Sartore, PhD ,
Gaetano Crepaldi, MD,
Achille C. Pessina, MD, PhD* and
Paolo Pauletto, MD*,*
* Dipartimento di Medicina Clinica e Sperimentale, Università di Padova, Italy
Dipartimento di Scienze Mediche e Chirurgiche, Università di Padova, Italy
Department of Medical Genetics, University of Washington, Seattle, Washington, USA
Dipartimento di Scienze Biomediche e Sperimentali, Università di Padova, Italy
Manuscript received December 12, 2001;
revised manuscript received June 5, 2002,
accepted June 12, 2002.
* Reprint requests and correspondence: Prof. Paolo Pauletto, Università degli Studi di Padova, Dipartimento di Medicina Clinica e Sperimentale, Via Giustiniani 2, 35128 Padova, Italy.
paolo.pauletto{at}unipd.it
OBJECTIVES: We investigated the potential association between –514 C T polymorphism in the promoter of the hepatic lipase gene (LIPC) and the prevalence of inflammatory cells in the plaque of patients with severe carotid artery stenosis.
BACKGROUND: This common LIPC polymorphism has been related to the presence of an atherogenic lipoprotein pattern.
METHODS: We studied 68 consecutive patients undergoing carotid endarterectomy. The LIPC genotype was determined by polymerase chain reaction. Endarterectomy specimens were examined by immunocytochemistry using monoclonal antibodies for smooth muscle cells, macrophages, or lymphocytes.
RESULTS: In 50 of 68 patients who had evidence of previous ipsilateral ischemic events, 36 (72%) were carriers of the CC genotype, whereas only 14 (28%) were carriers of the CT/TT genotype (p = 0.002). Among the 18 patients without evidence of events, the two genotypes were equally distributed (9 vs. 9). The low-density lipoprotein (LDL) particles were denser in CC than in CT/TT genotype carriers (flotation rate: 0.315 ± 0.025 vs. 0.356 ± 0.019, p < 0.0005). The CC genotype was associated with an abundance of macrophages (6.7 ± 3.5 vs. 2.1 ± 2.1 cells/area unit in the CT/TT group, p < 0.0005) and a reduced number of smooth muscle cells (6.9 ± 6.2 vs. 14.5 ± 6.4 in the CT/TT group, p < 0.0005) in the plaque. An inverse relationship was found between LDL buoyancy and the number of macrophages in the plaque (r = –0.639, p < 0.0005).
CONCLUSIONS: We provide evidence, for the first time, that LIPC promoter –514 CT polymorphism, by modulating LDL density, significantly affects the number of macrophages in the plaque and possibly affects the occurrence of cerebrovascular events in patients with carotid artery stenosis.
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Abbreviations and Acronyms
| | ANOVA | | analysis of variance | | apo | | apolipoprotein | | CARS | | Carotid Atherosclerosis and Restenosis Study | | CETP | | cholesteryl-ester transfer protein | | HDL | | high-density lipoprotein | | HL | | hepatic lipase | | LDL | | low-density lipoprotein | | LIPC | | hepatic lipase gene | | PCR | | polymerase chain reaction | | SMC | | smooth muscle cells |
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