A. S. Leon

The effect of sex, age and race on estimating percentage body fat from body mass index: The Heritage Family Study.

Objective: To study the effects of sex, age and race on the relation between body mass index (BMI) and measured percent body fat (%fat).Design: Cross-sectional validation study of sedentary individuals.Subjects: The Heritage Family Study cohort of 665 black and white men and women who ranged in age from 17 to 65 y.Measurements: Body density determined from hydrostatic weighing. Percentage body fat determined with gender and race-specific, two-compartment models. BMI determined from height and weight, and sex and race in dummy coded form.Results: Polynomial regression showed that the relationship between %fat and BMI was quadratic for both men and women. A natural log transformation of BMI adjusted for the non-linearity. Test for homogeneity of log transformed BMI and gender showed that the male–female slopes were within random variance, but the intercepts differed. For the same BMI, the %fat of females was 10.4% higher than that of males. General linear models analysis of the womens data showed that age, race and race-by-BMI interaction were independently related to %fat. The same analysis applied to the mens data showed that %fat was not just a function of BMI, but also age and age-by-BMI interaction. Multiple regression analyses provided models that defined the bias.Conclusions: These data and results published in the literature show that BMI and %fat relationship are not independent of age and gender. These data showed a race effect for women, but not men. The failure to adjust for these sources of bias resulted in substantial differences in the proportion of subjects defined as obese by measured %fat.

Generalized abdominal visceral fat prediction models for black and white adults aged 17–65 y: the HERITAGE Family Study

OBJECTIVE: To determine if the relationship between abdominal visceral fat (AVF) and measures of adiposity are different between Black and White subjects and to develop valid field prediction models that accurately identify those individuals with AVF levels associated with high risk for chronic disease.DESIGN: Cross-sectional measurements obtained from 91 Black men, 137 Black women, 227 White men, and 237 White women subjects, ages 17–65 y, who were participants in the HERITAGE Family Study, both at baseline and following 20 weeks of endurance training.MEASURMENTS: AVF, abdominal subcutaneous fat (ASF), abdominal total fat (ATF), and sagittal diameter (SagD) were measured by computed tomography (CT). Body density was determined by hydrostatic weighing and was used to estimate relative body fat. Arm, waist (WC), and hip circumferences and skinfold thickness measures were taken, and BMI was calculated from weight (kg) and height (m2). Since CT abdominal fat variables were skewed, a natural log transformation (Ln) was used to produce a normal distribution. The General Linear Model (GLM) procedure was used to test the relationship between AVF and two different groups of variables—CT and anthropometric.RESULTS: The AVF of White men and women was significantly higher than that of Black men and women, independent of BMI, WHR, WC, and age, and was greater for men than for women. The CT model showed that the combination of SagD, Ln (ASF), age, and race accounted for 84 and 75% of the variance in AVF in men and women, respectively. The anthropometric model provided two valid generalized field AVF prediction equations. The Field-I equation, which included BMI, WHR, age and race, had an r 2 of 0.78 and 0.73 for men and women, respectively. The Field-II equation, which included BMI (women only), WC, age, and race, had an r 2 of 0.78 and 0.72 for men and women, respectively. The field model equations became less accurate as the estimated AVF increased.CONCLUSIONS: (1) At the same age and level of adiposity, Black men and women have less AVF than White men and women. These differences are greater in men than in women. (2) The field regression equations can be generalized to the diverse group of adults studied, both in an untrained and trained state. However, their accuracy decreases with increasing levels of AVF.

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.SUBJECTS: Adult sedentary white (245 men and 258 women) and black (91 men and 185 women) subjects.MEASUREMENTS: 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 VO2max (FFA60%); and fasting insulin (INS).STATISTICAL ANALYSIS: 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%.CONCLUSION: 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.

Sex differences in the relationships of abdominal fat to cardiovascular disease risk among normal-weight white subjects

The objectives of this study are to investigate the relationships between abdominal fat and risk factors for cardiovascular disease (CVD) among normal-weight (NW) white subjects and to determine how these relationships differ by sex. NW adults (177 males and 258 females) and overweight adults (133 males and 111 females) from the Québec Family Study and the HERITAGE Family Study were retained for this study. Risk factors included systolic and diastolic blood pressures, low-density lipoprotein and high-density lipoprotein cholesterols, triglycerides, and fasting glucose. Only in NW female adults, abdominal visceral fat (AVF) area assessed by computed tomography was significantly correlated with all risk factors, except for fasting glucose, even after age, study cohort, and fat mass were taken into account. NW female subjects with at least one risk factor had a significantly higher AVF than those without risk factors, although the difference was small. Thus, only NW female adults with more AVF tended to have a more adverse CVD risk factor profile.

The agouti-related protein and body fatness in humans

OBJECTIVE: The objective of this study was to examine the impact of a single nucleotide polymorphism (SNP) (−38C>T) in the promoter of the human agouti-related protein (hAgRP) gene on promoter affinity for transcription factors (TFs) and its possible association with body composition phenotypes.DESIGN: Electrophoretic mobility shift assays for the functional studies and association analyses for the population studies.SUBJECTS AND METHODS: Nuclear extracts were isolated from the mouse hypothalamus cell line GT1-7 and subjected to binding assays using oligonucleotide probes corresponding to the −38C>T region and an antibody for the E12/E47 TFs. Individuals (n = 259) from the HERITAGE Family Study were genotyped for the −38C>T SNP and used in the association studies.RESULTS: Electrophoretic mobility shift and supershift assays confirmed binding of the E12/E47 TF to the −38C>T site in a genotype-dependent manner. The T allele was found exclusively in the black subjects while the genotype with the higher binding affinity, CC, was significantly associated with high BMI, fat mass, and percent body fat in the black subjects of the HERITAGE Family Study.CONCLUSIONS: The E12/E47 TF could play a role in the regulation of hAgRP expression while the population studies suggest that the TT genotype of the −38C>T SNP could play a protective role against the development of obesity in the black population of the HERITAGE Family Study.

Interactions among the β2- and β3- adrenergic receptor genes and total body fat and abdominal fat level in the HERITAGE Family Study

OBJECTIVE AND SUBJECTS: Interactions between markers in the β2- and β3-adrenergic receptor (ADR) genes and total body fat and computerized tomography-measured abdominal fat phenotypes were studied in the HERITAGE Family Study cohort of Black (n=205; 81 males and 124 females) and White (n=415; 198 males and 217 females) subjects before and after an endurance training program.RESULTS: In Black subjects, β2- and β3-ADR gene variants showed evidence of interactions on changes in total body fat mass and abdominal fat area (P<0.005 and =0.010, respectively). Black subjects who were carriers of both β2-ADR Arg16 and β3-ADR Arg64 alleles had a greater decrease in total fat mass as well as abdominal total and subcutaneous, but not visceral fat areas in response to endurance training than subjects with other genotype combinations (P from 0.011 to 0.047). After correction for multiple tests, the findings remained essentially unchanged for total body fat mass and abdominal fat area, but became nonsignificant for subcutaneous fat area. The changes in abdominal fat correlated positively with the changes in fat mass (P<0.0001). The interactions between β2 and β3-ADR gene markers accounted for a maximum of 3% of the variances in the response of total fat mass and abdominal fat area to endurance training in Black subjects but it was not significant in White subjects.CONCLUSION: Interactions between sequence variants in the β2–β3-ADR gene contributed to the changes in fat mass and abdominal adiposity in response to endurance training in Black subjects.

TITIN IS A CANDIDATE GENE FOR STROKE VOLUME RESPONSE TO ENDURANCE TRAINING: THE HERITAGE FAMILY STUDY

A genome-wide linkage scan for endurance training-induced changes in submaximal exercise stroke volume (DeltaSV50) in the HERITAGE Family Study revealed two chromosomal regions (2q31-q32 and 10p11.2) with at least suggestive evidence of linkage among white families. Here we report a further characterization of the quantitative trait locus (QTL) in chromosome 2q31 and provide evidence that titin (TTN) is likely a candidate gene involved. The original linkage was detected with two markers (D2S335 and D2S1391), and the QTL covered approximately 25 million base pairs (Mb). We added 12 microsatellite markers resulting in an average marker density of one marker per 2.3 Mb. The evidence of linkage increased from P = 0.006 to P = 0.0002 and 0.00002 in the multi- and single-point analyses, respectively. The strongest evidence of linkage was seen with two markers in and near the TTN gene. Transmission/disequilibrium test (TDT) with the same marker set provided evidence for association with one of the TTN markers (D2S385; P = 0.004). TTN is a major contributor to the elasticity of cardiomyocytes and a key regulator of the Frank-Starling mechanism. Since TTN is the largest gene in the human genome, the challenge is to identify the DNA sequence variants contributing to the interindividual differences in cardiac adaptation to endurance training.