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Human Molecular Genetics, 2000, Vol. 9, No. 9 1315-1320
© 2000 Oxford University Press

Evidence for a gene influencing the TG/HDL-C ratio on chromosome 7q32.3–qter: a genome-wide scan in the Framingham Study

Amanda M. Shearman1,+, Jose M. Ordovas2, L. Adrienne Cupples3, Ernst J. Schaefer2, Michael D. Harmon4, Yujun Shao3, J. Dianne Keen1, Anita L. DeStefano3,4, Oscar Joost4, Peter W. F. Wilson4, David E. Housman1 and Richard H. Myers4

1Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA, 2Lipid Metabolism Laboratory, USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA, 3School of Public Health and 4School of Medicine, Boston, MA 02118, USA

Some studies show that plasma triglyceride (TG) levels are a significant independent risk factor for cardiovascular disease (CVD). TG levels are inversely correlated with high density lipoprotein cholesterol (HDL-C) levels, and their metabolism may be closely interrelated. Therefore, the TG/HDL-C ratio may be a relevant CVD risk factor. Our analysis of families in the Framingham Heart Study gave a genetic heritability estimate for log(TG) of 0.40 and for log(TG/HDL-C) of 0.49, demonstrating an important genetic component for both. A 10 cM genome-wide scan for log(TG) level and log(TG/HDL-C) was carried out for the largest 332 extended families of the Framingham Heart Study (1702 genotyped individuals). The highest multipoint variance component LOD scores obtained for both log(TG) and log(TG/HDL-C) were on chromosome 7 (at 155 cM), where the results for the two phenotypes were 1.8 and 2.5, respectively. The 7q32.3–qter region contains several candidate genes. Four other regions with multipoint LOD scores greater than one were identified on chromosome 3 [LOD score for log(TG/HDL-C) = 1.8 at 140 cM], chromosome 11 [LOD score for log(TG/HDL-C) = 1.1 at 125 cM], chromosome 16 [LOD score for log(TG) = 1.5 at 70 cM, LOD score for log(TG/HDL-C) = 1.1 at 75 cM] and chromosome 20 [LOD score for log(TG/HDL-C) = 1.7 at 35 cM, LOD score for log(TG) = 1.3 at 40 cM]. These results identify loci worthy of further study.

+ To whom correspondence should be addressed. Tel: +1 617 253 3015; Fax: +1 617 253 5202; Email: shearman@mit.edu


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