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FTO affects changes in BMI during both childhood and adulthood. However, its effect on onset age of overweight in adulthood is not known. To address this question, we conducted a study to examine effects of FTO tag SNPs on censored age of overweight in the longitudinal Bogalusa Heart Study (BHS) cohort, which began in 1973-1974. Of participating subjects, 658 whites (308 males and 350 females) with genotype data were selected for the study. The FTO gene was examined by a survival analysis of 30 tag SNPs regarding their association with left, interval and right-censored adult overweight. After adjustment for birth weight and sex, SNP rs9939609 has a small nominal p value of 0.004 for the association with onset age, which has an expected proportion of false positives of 9.6 % after adjusting for multiple tests. It was estimated that genotypes AA, AT and TT have onset age (standard error) of 22.82 (1.07), 28.96 (1.04) and 27.76 (1.04) years, respectively, for a 50 % cumulative proportion of overweight in the population. Genotypes AA, AT and TT, respectively, have estimated survival probability of 65.8, 78.7 and 76.8 % at the age of 18; and survival probability of 6.5, 11.8 and 10.7 % at the age of 60. The odds ratios of survival beyond age ≥18 years are 0.52 for AA versus AT and 0.58 for AA versus TT. We thus concluded that risk genetic variants at FTO gene can accelerate the onset age and influence the survival odds of overweight in younger adults.

Objective To investigate possible age-related changes in associations between polymorphisms in the fat mass and obesity-associated (FTO) gene and higher body mass index (BMI). Design and Subjects Multilevel mixed regression models were used to examine associations between four FTO variants and longitudinal BMI profiles in non-Hispanic white and African American children and adolescents 8 - 17 years of age from two different longitudinal cohort studies, the Bogalusa Heart Study (BHS) and Project HeartBeat! (PHB). In the BHS, there were 1551 examinations of 478 African Americans and 3210 examinations of 1081 non-Hispanic whites; in PHB, there were 971 examinations of 131 African Americans and 4458 examinations of 505 non-Hispanic whites. Results In African Americans, no significant FTO associations with BMI were found. In non-Hispanic whites, linkage disequilibrium among all four variants made haplotype analysis superfluous, so we focused on the single-nucleotide polymorphism (SNP), rs9939609. In longitudinal multilevel models, the A/A genotype of rs9939609 was associated with higher BMI in non-Hispanic whites in both cohorts at all ages. A significant age-by-genotype interaction found only in the BHS cohort predicted that in those with the A/A genotype, BMI would be approximately 0.7 kg/m2 higher at age 8, and approximately 1.6 kg/m2 higher at age 17 than in those with A/T or T/T genotypes. The design of Project HeartBeat! limited follow-up of any single individual to four years, and may have reduced the ability to detect any age-by-genotype interaction in this cohort. Conclusions The A/A genotype of rs9939609 in the FTO gene is associated with higher longitudinal BMI profiles in non-Hispanic whites from two different cohorts. The association may change with age, with the A/A genotype being associated with a larger BMI difference in late adolescence than in childhood, though this was observed only in the Bogalusa Heart Study cohort and requires verification.

To investigate the influence of lipoprotein lipase (LPL) Ser447Stop and beta1-adrenergic receptor (ADRB1) Arg389Gly gene polymorphisms, individually and in combination, on obesity from childhood to adulthood.A community-based cohort of 1331 subjects (30% black and 70% white subjects) was followed over an average period of 23 years from childhood (age range: 4-17 years) to adulthood (age range:18-44 years).Body mass index (BMI, kg/m2) and LPL Ser447Stop and the ADRB1 Arg389Gly genotypes.The frequency of the ADRB1 Gly389 allele was 0.25 in white subjects vs 0.39 in black subjects (P0.001); 0.08 vs 0.05 (P = 0.280) for the LPL Stop447 allele. There was no association between the LPL Stop447 allele and BMI among white and black subjects either in childhood and adulthood levels or annual change from childhood to adulthood. The ADRB1 Gly389 allele was associated with lower BMI only in black adults (P = 0.017). Further, the interaction effect of the LPL Stop447 allele and ADRB1 Gly389 allele on adult BMI or its annual change was significant in white subjects and in the total sample (P = 0.03-0.006). Childhood values tended to show a similar trend. Having both ADRB1 Gly389 allele and LPL Stop447 allele was associated with 71% (95% confidence interval: 26-89%) less odds for developing obesity from childhood to adulthood after adjusting for age, race, sex, and childhood BMI.While Gly389 allele of the ADRB1 gene lowers obesity in black subjects, this allele in conjunction with Stop447 allele of the LPL gene lowers obesity in adults and attenuates the development of obesity from childhood to adulthood. These findings underscore the importance of gene-gene interaction in the assessment of genetic influences on complex traits such as obesity.

OBJECTIVE: Although obese children are at increased risk for coronary heart disease in later life, it is not clear if this association results from the persistence of childhood obesity into adulthood. We examined the relation of adiposity at various ages to the carotid intima-media thickness (IMT) at age 35 y. DESIGN: Prior to the determination of IMT by B-mode ultrasound, subjects (203 men, 310 women) had, on average, six measurements of body mass index (BMI) and triceps skinfold thickness (TSF) between the ages of 4 and 35 y. Mixed regression models for longitudinal data were used to assess the relation of these characteristics to adult IMT. RESULTS: Overall, adult IMT was associated with levels of both BMI and TSF (P

To examine the longitudinal changes in adiposity and related risk variables of Syndrome X from childhood to young adulthood with respect to early onset of menarche.Community-based longitudinal cohort of female subject (65% white, 35% blacks subjects) who participated in two or more surveys from childhood to young adulthood and had reported their menarcheal age (12 y, n=437 vsor =12 y, n=1042).In childhood (5-11 y), adolescence (12-18 y), and young adulthood (19-37 y), females with early menarche displayed significantly higher body mass index (BMI) and triceps skinfold thickness; higher stature in childhood and adolescence; higher fasting insulin and homeostasis model assessment index of insulin resistance (HOMA-IR) in childhood and adulthood; and higher fasting glucose in adulthood. Blood pressure and lipoprotein variables showed no early menarche-related differences. Longitudinal rates of change in BMI (P=0.002), triceps skinfold thickness (P=0.05), insulin (P=0.09), and HOMA-IR (P=0.05) were positive and faster among female subjects with early menarche; fasting glucose decreased slowly in this group (P=0.006). In a multivariate analysis, body fatness and insulin related independently to early menarche (P0.001). This association was stronger in white subjects (P=0.0008). In adulthood, the prevalence of clustering of three to four risk factors of syndrome X (highest quartile of: (1) BMI, (2) fasting insulin, (3) systolic or mean arterial pressure, and (4) total cholesterol to HDL cholesterol or triglycerides to HDL cholesterol ratio specific for age, race, and study year) was higher among those with early menarche (10.7 vs 6.2%, P=0.002). The odds for developing such clustering in adulthood among those with early menarche was 1.54 (95% CI=1.14-2.07), regardless of race.Early menarche is characterized by excess body fatness and insulin beginning in early childhood and higher prevalence of clustering of adverse levels of risk variables of metabolic Syndrome X in young adulthood.

To assess the association of childhood parental history of type 2 diabetes and the risk of diabetes in adulthood. Observations were made on a community-based cohort of normoglycemic (n = 1619), pre-diabetic (n = 78), and type 2 diabetic (n = 50) adult subjects followed serially for cardiovascular risk factors over 22 years from childhood and noting their relation to a parental history of diabetes. In a longitudinal multivariate model including parental diabetes observed in the offspring's childhood, BMI, MAP, HDL cholesterol, LDL cholesterol, triglycerides, insulin, and glucose, adjusted for age, age(2), race, sex, and race by sex interaction, parental diabetes and adverse changes in LDL cholesterol and glucose were independently associated with pre-diabetic status in adulthood (regression coefficient [beta] = 0.74 (95% CI: 0.04-1.45), 0.44 (95% CI: 0.24-0.64), and 1.99 (95% CI: 1.73-2.25), respectively), while parental diabetes and adverse changes in BMI, HDL cholesterol, and glucose were associated with the diabetic status (beta = 1.14 (95% CI: 0.35-1.92), 0.08 (95% CI: 0.05-0.11), -0.51 (95% CI: -1.03 to -0.003), and 1.79 (95% CI: 1.48-2.09), respectively). Childhood parental history of diabetes along with adverse changes in adiposity, glucose, and lipoprotein variables of metabolic syndrome since childhood are associated with the increased risk of pre-diabetic and diabetic status in adulthood.

Background Conflicting information exists regarding the association between hsCRP and the progression of early stages of atherosclerosis. The purpose of the study was to investigate the association of high sensitiviy c-reactive protein (hsCRP) along with major cardiovascular (CV) risk factors on early carotid atherosclerosis progression in a large, population-based cohort study. Methods The study cohort included 839 young adults (aged 24 to 43 years, 70% white, 42% men) enrolled in Bogalusa Heart Study, who in 2001-2002 attended baseline examination with measurements of CV risk factors. Progression of carotid artery intima-media thickness (IMT) was assessed during a mean follow-up of 2.4 years. Results Carotid artery IMT progression rates were as follows: composite carotid artery = 9.2 ± 52 μm/y, common carotid artery = 0.0 ± 51 μm/y, carotid bulb = 8.8 ± 103 μm/y, and internal carotid artery = 18.9 ± 81 μm/y. Elevated baseline hsCRP, reflecting an inflammatory state, showed independent association with composite carotid artery IMT progression. Increased age, systolic blood pressure, fasting glucose, LDL cholesterol, and current smoking were other risk associates of carotid artery IMT progression in young adults, indicating an underlying burden on the CV system by multiple risk factors. Conclusion In this population-based study, we observed independent categorical association of increased hsCRP with carotid artery IMT progression in young adults. This study underlines the importance of assesssing hsCRP levels along with smoking and traditional CV risk factor profiles in asymptomatic young adults.

Background Several studies have linked low birth weight to adverse levels of cardiovascular risk factors and related diseases. However, information is sparse at a community level in the U.S. general population regarding the effects of low birth weight on the longitudinal trends in cardiovascular risk factor variables measured concurrently from childhood to adolescence. Methods Longitudinal analysis was performed retrospectively on data collected from the Bogalusa Heart Study cohort (n = 1141; 57% white, 43% black) followed from childhood to adolescence by repeated surveys between 1973 and 1996. Subjects were categorized into low birth weight (below the race-specific 10th percentile; n = 123) and control (between race-specific 50–75th percentile; n = 296) groups. Results Low birth weight group vs control group had lower mean HDL cholesterol (p = 0.05) and higher LDL cholesterol (p = 0.05) during childhood (ages 4–11 years); higher glucose (p = 0.02) during adolescence. Yearly rates of change from childhood to adolescence in systolic blood pressure (p = 0.02), LDL cholesterol (p = 0.05), and glucose (p = 0.07) were faster, and body mass index (p = 0.03) slower among the low birth weight group. In a multivariate analysis, low birth weight was related independently and adversely to longitudinal trends in systolic blood pressure (p = 0.004), triglycerides (p = 0.03), and glucose (p = 0.07), regardless of race or gender. These adverse associations became amplified with age. Conclusions Low birth weight is characterized by adverse developmental trends in metabolic and hemodynamic variables during childhood and adolescence; and thus, it may be an early risk factor in this regard.

EARLIER investigations on glycoproteins from connective tissue have been mainly concerned with their chemical characteristics1–6, but very little is known about the biological function of this group of glycoproteins. Our previous observations7 demonstrated the presence of a family of glycoproteins in cardiovascular connective tissue which varied from individual to individual and suggested a genetic basis for their differences. We have isolated glycoproteins from aorta, skin and kidney of bovine, ovine, and human twins and analysed by gel electrophoresis to determine whether variations in glycoproteins occurred among identical and nonidentical twin pairs. Because connective tissue glycoproteins also show enzymatic activities like esterase and phosphatase8, zymograms for these two enzymes were also obtained on polyacrylamide gels. The glycoprotein samples were analysed further by immunoelectrophoresis because they are highly antigenic3–7.