title: 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% in LIPC-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.
authors.affiliation: Department of Preventive Medicine and Biometrics, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA. john.hokanson@UCHSC.edu
authors.forename: John E
authors.initials: JE
authors.lastname: Hokanson
authors.forename: Suzanne
authors.initials: S
authors.lastname: Cheng
authors.forename: Janet K
authors.initials: JK
authors.lastname: Snell-Bergeon
authors.forename: Bonnie A
authors.initials: BA
authors.lastname: Fijal
authors.forename: Michael A
authors.initials: MA
authors.lastname: Grow
authors.forename: Chi
authors.initials: C
authors.lastname: Hung
authors.forename: Henry A
authors.initials: HA
authors.lastname: Erlich
authors.forename: James
authors.initials: J
authors.lastname: Ehrlich
authors.forename: Robert H
authors.initials: RH
authors.lastname: Eckel
authors.forename: Marian
authors.initials: M
authors.lastname: Rewers
mesh_terms: D000328:Adult; D017668:Age of Onset; D002114:Calcinosis / Q000503:physiopathology*; D008076:Cholesterol, HDL / Q000097:blood; D003120:Colorado; D003327:Coronary Disease / Q000503:physiopathology*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005787:Gene Frequency; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007328:Insulin; D008049:Lipase / Q000235:genetics*; D008099:Liver / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D014280:Triglycerides / Q000097:blood; D044465:White People
chemical_list: D008076:Cholesterol, HDL; D006442:Glycated Hemoglobin; D007328:Insulin; D008049:Lipase; D014280:Triglycerides