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


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.
Fan
Y M
YM
Laboratory of Atherosclerosis Genetics, Centre for Laboratory Medicine, Tampere University Hospital and Medical School, University of Tampere, Finland. loyufa@uta.fi
Lehtimäki
T
T
Rontu
R
R
Ilveskoski
E
E
Goebeler
S
S
Kajander
O
O
Mikkelsson
J
J
Viiri
L E
LE
Perola
M
M
Karhunen
P J
PJ
D000328:Adult; D000368:Aged; D001344:Autopsy / Q000379:methods; D003324:Coronary Artery Disease / Q000235:genetics*; D003645:Death, Sudden / Q000209:etiology*; D006801:Humans; D008049:Lipase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors
C504173:LIPC protein, human; D008049:Lipase