The hepatic lipase gene C-480T polymorphism in the development of early coronary atherosclerosis: the Helsinki Sudden Death Study

• Published in: European journal of clinical investigation Vol. 37; no. 6; pp. 472 - 477
• Main Authors: Fan, Y. M., Lehtimäki, T., Rontu, R., Ilveskoski, E., Goebeler, S., Kajander, O., Mikkelsson, J., Viiri, L. E., Perola, M., Karhunen, P. J.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.06.2007; Blackwell
• Subjects: Adult; Aged; Atherosclerosis; Atherosclerosis (general aspects, experimental research); Autopsy - methods; autopsy study; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Coronary Artery Disease - genetics; Death, Sudden - etiology; fatty streak; General aspects; hepatic lipase; Humans; Lipase - genetics; Male; Medical sciences; Middle Aged; polymorphism; Polymorphism, Genetic - genetics; Risk Factors; Cardiocirculatory arrest; Genetic variability; fatty streak; Enzyme; Liver; Sudden death; Coronary artery; hepatic lipase; Triacylglycerol lipase; Cardiovascular disease; Genotype; Esterases; Coronary heart disease; autopsy study; Carboxylic ester hydrolases; Vascular disease; Medicine; Autopsy; Atherosclerosis; Development; Hydrolases; Early; Polymorphism
• ISSN: 0014-2972; 1365-2362
• DOI: 10.1111/j.1365-2362.2007.01812.x

Background  The T allele of the hepatic lipase (HL) C‐480T polymorphism was previously found to be associated with lower post‐heparin plasma HL activity, atherosclerosis and risk of coronary artery disease. We studied the association of HL C‐480T polymorphism with the extent of atherosclerosis at vessel‐wall level in an autopsy series of middle‐aged men. Materials and methods  An autopsy cohort of 700 Caucasian Finnish men aged 33–70 years (mean 53 years), which comprised two autopsy series, collected 10 years apart during 1981–82 and 1991–92, were analysed. Areas of coronary wall covered with fatty streaks and fibrotic and complicated lesions were measured using computer‐assisted planimetry and related to HL C‐480T genotypes (CC, CT, and TT). Results  There was a significant age–by–genotype interaction on the mean percentage area of fatty streaks (P = 0·01). The HL C‐480T polymorphism was a significant explanatory factor for fatty streak area in men under 53 years of age with or without age, body mass index, hypertension, diabetes, smoking, alcohol consumption, apolipoprotein E genotype, and series number as covariates. Men carrying the TT genotype had two times larger areas of fatty streaks compared to the CC carriers (8·8% vs. 4·3%, P = 0·009). However, this association disappeared in men over 53 years. The areas of more advanced atherosclerotic lesions did not vary significantly among the genotype groups. Conclusions  Our results suggest that the HL C‐480T polymorphism affects the formation of early coronary atherosclerotic lesions in men in their early middle age.