Genetic variation in the hepatic lipase gene and the risk of coronary heart disease among US diabetic men: potential interaction with obesity.
OBJECTIVE
The -514 C to T polymorphism of the hepatic lipase gene (LIPC) has been associated with lowered LIPC activity and elevated HDL-cholesterol concentrations. Previous findings on the association of this polymorphism with the risk of CHD are inconsistent. Moreover, data on this association among diabetic patients are limited. We investigated the association of the LIPC polymorphism with CHD risk among US diabetic men and evaluated whether this association was modified by adiposity status.


METHODS
The case group consisted of 220 diabetic men who were recruited from the Health Professionals Follow-up Study (years 1986-2000) and were free of cardiovascular disease at baseline, but subsequently developed CHD. A total of 641 diabetic men from the same study but without cardiovascular disease constituted the control group.


RESULTS
No overall association between the LIPC polymorphism and CHD risk was observed. However, we did observe a significant interaction between this polymorphism and BMI in association with CHD risk. Among obese men, after adjustment for age, duration of diabetes and major lifestyle factors, the CT or TT genotype was associated with an increased CHD risk compared with the CC genotype (odds ratio [OR] 2.52, 95% CI 1.08-5.90); the corresponding ORs (95% CI) were 0.99 (0.58, 1.69) for overweight men (25< or =BMI <30 kg/m(2)) and 0.37 (0.17, 0.79) for lean men (BMI <25 kg/m(2)) (p for interaction 0.001). Stratified analyses by waist circumference (tertiles) showed a similar pattern of interaction (adjusted p for interaction 0.023).


CONCLUSIONS
These data suggest that obesity may modify the association between the LIPC C(-514)T polymorphism and CHD risk among diabetic men.
Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA, 02115, USA. nhcui@channing.harvard.edu
C
C
Zhang
R
R
Lopez-Ridaura
E B
EB
Rimm
T
T
Li
D J
DJ
Hunter
F B
FB
Hu
D000328:Adult; D000368:Aged; D003327:Coronary Disease / Q000209:etiology / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics; D003925:Diabetic Angiopathies / Q000209:etiology / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008019:Life Style; D008049:Lipase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014481:United States
C504173:LIPC protein, human; D008049:Lipase