A common promoter polymorphism in the hepatic lipase gene (LIPC-480C>T) is associated with an increase in coronary calcification in type 1 diabetes

Abstract

Type 1 diabetes is associated with coronary heart disease (CHD) and coronary artery calcification (CAC), a measure of subclinical CHD. The hepatic lipase gene promoter polymorphism (LIPC-480C>T) is a common variant affecting lipid metabolism. This study examined the relation between the LIPC-480C>T and CAC in type 1 diabetes. In the type 1 diabetic patients studied, 56% had CAC >0 Agatston units (AU). These subjects had a longer duration of diabetes (26.2 ± 1.3 vs. 17.8 ± 1.4 years; P < 0.001), lower HDL cholesterol levels (55.7 ± 2.4 vs. 61.0 ± 2.5 mg/dl; P = 0.05), higher triglyceride levels (101 ± 17.3 vs. 66 ≥ 7.6 mg/dl; P < 0.05), and higher diastolic blood pressure (79.7 ± 1.0 vs. 76.0 ± 1.4 mmHg; P < 0.05). The LIPC-480 T allele was more common in subjects with CAC (frequency = 0.31 ± 0.05 vs. 0.14 ± 0.04; P = 0.006). The proportion with CAC was 44% inLIPC-480CC subjects, 71% in heterozygotes, and 83% in LIPC-480TT subjects (P < 0.01). LIPC-480 T allele frequency increased as the amount of CAC increased (P = 0.007). LIPC-480 genotype was independently associated with the CAC (odds ratio = 2.90, 95% CI 1.22-6.92, P < 0.05) after adjusting for duration of diabetes, age, sex, diastolic blood pressure, HDL cholesterol, and triglyceride levels. In conclusion, the LIPC-480C>T polymorphism was associated with subclinical CHD in type 1 diabetes. This genetic variant may identify subjects in which early intervention to prevent CHD may be appropriate.