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* Department of Epidemiology and Institute for Public Health Genetics, School of Public Health and Community Medicine, University of Washington, Seattle, WA
Department of Biostatistics, School of Public Health and Community Medicine, University of Washington, Seattle, WA
Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, University of Washington, Seattle, WA
** Departments of Medicine and Genome Sciences, University of Washington, Seattle, WA
Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX
Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX
1 To whom correspondence should be addressed. e-mail: maustin{at}u.washington.edu
Small, dense LDLs and hypertriglyceridemia, two highly correlated and genetically influenced risk factors, are known to predict for risk of coronary heart disease. The objective of this study was to perform a whole-genome scan for linkage to LDL size and triglyceride (TG) levels in 26 kindreds with familial hypertriglyceridemia (FHTG). LDL size was estimated using gradient gel electrophoresis, and genotyping was performed for 355 autosomal markers with an average heterozygosity of 76% and an average spacing of 10.2 centimorgans (cMs). Using variance components linkage analysis, one possible linkage was found for LDL size [logarithm of odds (LOD) = 2.1] on chromosome 6, peak at 140 cM distal to marker F13A1 (closest marker D6S2436). With adjustment for TG and/or HDL cholesterol, the LOD scores were reduced, but remained in exactly the same location. For TG, LOD scores of 2.56 and 2.44 were observed at two locations on chromosome 15, with peaks at 29 and 61 cM distal to marker D15S822 (closest markers D15S643 and D15S211, respectively). These peaks were retained with adjustment for LDL size and/or HDL cholesterol.
These findings, if confirmed, suggest that LDL particle size and plasma TG levels could be caused by two different genetic loci in FHTG.
Supplementary key words cardiovascular disease • hyperlipidemia • genetic mapping
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