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

Some studies show that plasma triglyceride (TG) levels are a significant in dependent risk factor for cardiovascular disease (CVD). TG levels are inver sely correlated with high density lipoprotein cholesterol (HDL-C) levels, a nd their metabolism may be closely interrelated. Therefore, the TG/HDL-C ra tio may be a relevant CVD risk factor. Our analysis of families in the Fram ingham 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 componen t for both. A 10 cM genome-wide scan for log(TG) level and log(TG/HDL-C) wa s carried out for the largest 332 extended families of the Framingham Heart Study (1702 genotyped individuals). The highest multipoint variance compon ent LOD scores obtained for both log(TG) and log(TG/ HDL-C) were on chromos ome 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, F our other regions with multipoint LOD scores greater than one were identifi ed on chromosome 3 [LOD score for log(TG/HDL-C) = 1.8 at 140 cM], chromosom e 11 [LOD score for log(TG/HDL-C) = 1.1 at 125 cM], chromosome 16 [LOD scor e for log(TG) = 1.5 at 70 cM, LOD score for log(TG/HDL-C) = 1.1 at 75 cM] a nd 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 stu dy.