The hormone-sensitive lipase gene and body composition: the HERITAGE Family Study.
OBJECTIVE
To investigate whether the C-60G polymorphism and other markers in the hormone-sensitive lipase (LIPE) gene are associated with baseline body composition and free-fatty acid (FFA) concentrations measured at rest and during low-intensity exercise in white and black subjects participating in the HERITAGE Family Study.


METHODS
Adult sedentary white (245 men and 258 women) and black (91 men and 185 women) subjects.


METHODS
body mass index (BMI); fat mass (FAT); percentage body fat (%FAT); fat-free mass (FATFR); sum of eight skinfolds (SF8); subcutaneous (ASF), visceral (AVF) and total (ATF) abdominal fat areas assessed by CT scan; plasma FFA concentrations measured at rest (FFAR), at a power output of 50 W (FFA50) and at a relative power output of 60% of VO(2max) (FFA60%); and fasting insulin (INS).


METHODS
Association between the C-60G polymorphism of the LIPE gene and each phenotype was tested separately in men and women using ANCOVA with the effects of age and race as covariates and with further adjustment for FAT for ASF, AVF, ATF, FFAR, FFA50 and FFA60%. Secondly, owing to significant gene-by-race interaction, associations were investigated separately in each of the two race groups. Linkage was tested with the C-60G polymorphism, a dinucleotide repeat polymorphism in the intron 7 of the LIPE gene and two microsatellites markers (D19S178 and D19S903) flanking the LIPE gene.


RESULTS
There were no race differences in the allele frequencies of the C-60G polymorphism of the LIPE gene. No association or gene-by-race interaction was observed in men. However, in women, strong gene-by-race interactions were observed for BMI (P=0.0005), FAT (P=0.0007), %FAT (P=0.0003), SF8 (P=0.0001), ASF (P=0.03) and ATF (P=0.01). When the analysis was performed separately in each race, white women carriers of the -60G allele exhibited lower %FAT (P=0.005) and SF8 (P=0.01) than non-carriers, while in black women, the -60G allele was associated with higher BMI (P=0.004), FAT (P=0.009), %FAT (P=0.01) and SF8 (P=0.0009). These associations were no longer significant after adjusting for INS. Evidence of linkage was observed in whites with ATF, FFAR, FFA50 and FFA60%.


CONCLUSIONS
These results suggest that the C-60G polymorphism in the LIPE gene plays a role in determining body composition and that its effect is sex-, race- and insulin-dependent.
Garenc
C
C
Division of Kinesiology, Department of Preventive Medicine, Laval University, Ste-Foy, Québec, Canada.
Pérusse
L
L
Chagnon
Y C
YC
Rankinen
T
T
Gagnon
J
J
Borecki
I B
IB
Leon
A S
AS
Skinner
J S
JS
Wilmore
J H
JH
Rao
D C
DC
Bouchard
C
C
D000005:Abdomen; D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D000886:Anthropometry; D044383:Black People; D001798:Blood Proteins; D001823:Body Composition / Q000235:genetics*; D015992:Body Mass Index; D017931:DNA Primers; D005080:Exercise Test; D005192:Family Health; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005784:Gene Amplification; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012867:Skin; D012885:Skinfold Thickness; D002787:Sterol Esterase / Q000235:genetics*; D044465:White People
D001798:Blood Proteins; D017931:DNA Primers; D005230:Fatty Acids, Nonesterified; D002787:Sterol Esterase