Influence of the beta2-adrenergic receptor Arg16Gly polymorphism on longitudinal changes in obesity from childhood through young adulthood in a biracial cohort: the Bogalusa Heart Study.

BACKGROUND: The beta2-adrenergic receptor (ADRB2) plays a major role in regulating energy expenditure by stimulating lipid metabolism in human adipose tissue. Polymorphisms in the ADRB2 gene have been associated with obesity and various weight-related traits in cross-sectional studies of adults, but little is known about the effects of the ADRB2 gene on childhood obesity or the propensity to gain weight over time. OBJECTIVE: To assess the effects of a polymorphism in codon 16 (Arg16-->Gly) of the ADRB2 gene, which has been associated with a decrease in beta2-receptor density and efficiency, on longitudinal changes in obesity from childhood to young adulthood in a biracial cohort. DESIGN: Seven cross-sectional screenings of children and five cross-sectional screenings of young adults who were previously examined as children produced longitudinal data from childhood to young adulthood. METHODS: Height, weight and subscapular and triceps skinfolds were measured by trained examiners following identical protocols over the course of the study. Gender- and age-stratified analyses using random coefficients models were used to examine longitudinal genetic effects on obesity in 1151 African-American and Caucasian males and females who attended an average of six examinations over a 24 y period from childhood to young adulthood. RESULTS: Age-stratified analyses showed no clear genetic relationships with changes in obesity measures over time in females, but an age-dependent association was observed in males, where the relationship between the Arg16Gly polymorphism and obesity became stronger with age. In males who were 4-9 y of age at the beginning of the study in 1973, body mass index (BMI) was 4% higher in Gly/Gly and Arg/Gly males compared to those with Arg/Arg by 26 y of age. Subscapular skinfold measurements in Gly/Gly males became significantly different from Arg/Arg males (20% higher) by age 20. In the oldest male cohort (10-14 y of age in 1973), BMI increased at a significantly greater rate (0.4%/y) in males carrying the Gly16 form of the receptor relative to Arg/Arg males. BMI was significantly different between homozygous genotypes by approximately 26 y of age, and reached 8% higher in Gly/Gly males by age 32. Subscapular skinfolds also increased at a significantly greater rate (2%/y) in Gly/Gly males compared to Arg/Arg males, becoming significantly different (27%) by approximately 22 y of age and reaching a maximum difference of 50% by age 32. CONCLUSIONS: Our data suggest that the beta2-adrenergic receptor is associated with the propensity to gain weight from childhood to young adulthood in males. An increased understanding of genetic influences on the development of obesity may improve the effectiveness of interventions designed to reduce excess body weight and help define the role of genetic factors in diabetes and cardiovascular disease.

Coronary heart disease prediction from lipoprotein cholesterol levels, triglycerides, lipoprotein(a), apolipoproteins A-I and B, and HDL density subfractions: The Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Despite consensus on the need for blood cholesterol reductions to prevent coronary heart disease (CHD), available evidence on optimal cholesterol levels or the added predictive value of additional lipids is sparse. METHODS AND RESULTS: After 10 years follow-up of 12 339 middle-aged participants free of CHD in the Atherosclerosis Risk in Communities Study (ARIC), 725 CHD events occurred. The lowest incidence was observed in those at the lowest LDL cholesterol (LDL-C) quintile, with medians of 88 mg/dL in women and 95 mg/dL in men, and risk accelerated at higher levels, with relative risks (RRs) for the highest quintile of 2.7 in women and 2.5 in men. LDL-C, HDL-C, lipoprotein(a) [Lp(a)], and in women but not men, triglycerides (TG) were all independent CHD predictors, providing an RR, together with blood pressure, smoking, and diabetes, of 13.5 in women and 4.9 in men. Lp(a) was less significant in blacks than whites. Prediction was not enhanced by HDL-C density subfractions or apolipoproteins (apo) A-I or B. Despite strong univariate associations, apoB did not contribute to risk prediction in subgroups with elevated TG, with lower LDL-C, or with high apoB relative to LDL-C. CONCLUSIONS: Optimal LDL-C values are <100 mg/dL in both women and men. LDL-C, HDL-C, TG, and Lp(a), without additional apolipoproteins or lipid subfractions, provide substantial CHD prediction, with much higher RR in women than men.

Metabolic and lifestyle determinants of postprandial lipemia differ from those of fasting triglycerides: The Atherosclerosis Risk In Communities (ARIC) study.

Despite the reported association of lipoprotein responses to a fatty meal with atherosclerosis, little is known about the determinants of these responses. Plasma triglyceride, retinyl palmitate, and apolipoprotein B-48 responses to a standardized fatty meal containing a vitamin A marker were measured in 602 Atherosclerosis Risk in Communities (ARIC) study participants. To focus on postprandial responses specifically, which have been reported to be related to atherosclerosis independently of fasting triglycerides, analyses for determinants of postprandial responses were adjusted for fasting triglycerides. Major determinants of fasting triglycerides, namely, diabetes, obesity, other factors related to insulin resistance, and male sex, were not independently associated with postprandial responses. Fasting triglycerides were the strongest predictor of postprandial lipids, but independent of triglycerides, the predictors of postprandial responses were smoking, diet, creatinine, and alcohol. Smokers had substantially increased retinyl palmitate and apolipoprotein B-48 responses, indicators of chylomicrons and their remnants. Persons who consume more calories or omega3 fatty acids had reduced chylomicron responses. Triglyceride responses were associated positively with serum creatinine levels and negatively with moderate alcohol consumption. Thus, determinants of fasting and postprandial lipids differ. The independent atherogenic influence of postprandial lipids may relate more to smoking and diet than to obesity and insulin resistance.

Validation of death certificate diagnosis for coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) Study.

The validity of the death certificate in identifying coronary heart disease deaths was evaluated using data from the community surveillance component of the Atherosclerosis Risk in Communities Study (ARIC). Deaths in the four ARIC communities of Forsyth Co., NC; Jackson, MS; Minneapolis, MN; and Washington Co., MD were selected based on underlying cause of death codes as determined by the rules of the ninth revision of the International Classification of Diseases (ICD-9). Information about the deaths was gathered through informant interviews, physician or coroner questionnaires, and medical record abstraction, and was used to validate the cause of death. Sensitivity, specificity, and positive predictive value of the death certificate classification of CHD death (ICD-9 codes 410-414 and 429.2) were estimated by comparison with the validated cause of death based on physician review of all available information. Results from 9 years of surveillance included a positive predictive value 0.67 (95% CI 0.66-0.68), sensitivity of 0.81 (95% CI 0.79-0.83), and a false-positive rate (1-specificity) of 0.28 (95% CI 0.26-0.30). Comparing CHD deaths as defined by the death certificate with validated CHD deaths indicated that the death certificate overestimated CHD mortality by approximately 20% in the ARIC communities. Within subgroups, death certificate overestimation was reduced with advancing age (up to age 74), was consistent over time, was not dependent on gender, and exhibited considerable variation among communities.