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Hepatic lipase gene variation is related to coronary reactivity in healthy young men
Y Fan1, R Laaksonen, T Janatuinen
1Tampere University Hospital and University of Tampere, Medical School, Tampere, Finland.
Insights
The hepatic lipase (HL) gene C-480T polymorphism is linked to coronary artery function in healthy men. High activity HL genotypes show improved coronary flow reserve (CFR), suggesting a role in early cardiovascular disease development.
Area of Science:
- Cardiovascular Genetics
- Molecular Cardiology
- Vascular Physiology
Background:
- Impaired coronary flow reserve (CFR) indicates vascular dysfunction preceding angiographic lesions.
- Hepatic lipase (HL) gene C-480T polymorphism influences HL activity, with controversial links to coronary artery disease.
- The effect of HL genotypes on coronary function remains unstudied.
Purpose of the Study:
- To investigate the association between HL genotypes and coronary artery function in healthy young men.
- To determine if HL gene polymorphism impacts coronary reactivity.
Main Methods:
- Study included 49 healthy, mildly hypercholesterolemic men (mean age 35 years).
- Myocardial blood flow assessed using positron emission tomography with [15O] H2O at rest and during hyperemia.
- HL genotype determined via PCR and Nla III enzyme digestion.
Main Results:
- No significant difference in resting myocardial blood flow between high and low activity HL genotypes.
- Coronary flow reserve (CFR) was 24% higher in men with the high activity genotype (n=26) versus low activity (n=23).
- HL genotype independently predicted CFR in multivariate analysis (P=0.038).
Conclusions:
- The HL gene C-480T polymorphism may modulate coronary reactivity in healthy young men.
- This polymorphism could reflect early coronary dysfunction pathogenesis.
- Further research is needed to confirm if HL polymorphism is a cardiovascular disease risk factor in dyslipoproteinemic populations.
Background:
Impaired coronary flow reserve (CFR) can be used to indicate vascular dysfunction before the appearance of angiographic lesions. The hepatic lipase (HL) gene has a functional promoter polymorphism at position C-480T, which affects transcription and leads to high activity (C/C) and low activity (C/T, T/T) genotypes. These genotypes modulate HL activity, but their role in coronary artery disease is controversial and the effect on coronary function has not been studied. We investigated whether HL genotypes are associated with coronary artery function in healthy young men.
Materials And Methods:
We studied 49 healthy, mildly hypercholesterolemic men (aged 35 +/- 4 years). Myocardial blood flow was measured at rest and during adenosine induced hyperaemia with positron emission tomography using [15O] H2O. HL genotype was determined by PCR and Nla III enzyme digestion.
Results:
Resting myocardial blood flow was not statistically different in subjects with high and low activity HL genotypes. However, CFR (the ratio of adenosine flow to resting flow) was 24% higher (4.62 +/- 1.52 vs. 3.73 +/- 1.08 mL g-1 min-1, P = 0.024) in men with the high activity genotype (n = 26) than in those with low activity (n = 23). In multivariate analysis, the HL genotype remained a significant predictor of CFR (P = 0.038) after adjusting for age, body mass index, serum lipids and smoking.
Conclusions:
The findings of our preliminary study suggest that the C-480T polymorphism of the HL gene may modify coronary reactivity and reflect differences in the early pathogenesis of coronary dysfunction in these healthy young men. If the association between HL polymorphism and impaired CFR is also present in subjects with other dyslipoproteinemias, the HL polymorphism could be a new risk factor for cardiovascular disease.