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 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.
Shearman
A M
AM
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA, shearman@mit.edu
Ordovas
J M
JM
Cupples
L A
LA
Schaefer
E J
EJ
Harmon
M D
MD
Shao
Y
Y
Keen
J D
JD
DeStefano
A L
AL
Joost
O
O
Wilson
P W
PW
Housman
D E
DE
Myers
R H
RH
D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000097:blood* / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood* / Q000235:genetics*; D002897:Chromosomes, Human, Pair 7; D015331:Cohort Studies; D005260:Female; D008040:Genetic Linkage; D015894:Genome, Human; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D014280:Triglycerides / Q000097:blood* / Q000235:genetics*
D008076:Cholesterol, HDL; D014280:Triglycerides