A Common Promoter Polymorphism in the Hepatic Lipase Gene (LIPC-480C>T) Is Associated With an Increase in Coronary Calcification in Type 1 Diabetes

  1. John E. Hokanson1,
  2. Suzanne Cheng2,
  3. Janet K. Snell-Bergeon1,
  4. Bonnie A. Fijal2,
  5. Michael A. Grow2,
  6. Chi Hung2,
  7. Henry A. Erlich2,
  8. James Ehrlich3,
  9. Robert H. Eckel4 and
  10. Marian Rewers1
  1. 1Department of Preventive Medicine and Biometrics, University of Colorado Health Sciences Center, Denver, Colorado
  2. 2Roche Molecular Systems, Alameda, California
  3. 3Colorado Heart Imaging, Denver, Colorado
  4. 4Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado

    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.

    Footnotes

    • Address correspondence and reprint requests to John E. Hokanson, PhD, Department of Preventive Medicine and Biometrics, University of Colorado Health Sciences Center, Box C245, 4200 East 9th Ave., Denver, CO 80262. E-mail: john.hokanson{at}UCHSC.edu.

      Received for publication 17 September 2001 and accepted in revised form 4 January 2002.

      AU, Agatston unit; CAC, coronary artery calcification; CHD, coronary heart disease; EBCT, electron-beam computed tomography; HU, Hounsfield unit; IDL, intermediate-density lipoprotein; LIPC-480C>T, hepatic lipase gene promoter polymorphism; OR, odds ratio; SNP, single nucleotide polymorphism.

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