Abstract-Oxidative stress plays important roles in a wide spectrum of pathological processes, such as atherosclerosis.Although several environmental factors are documented to influence redox metabolism, relatively little is known about genetic effects. In the present study, we evaluated genetic contributions to variation in plasma total antioxidant status (TAS), a measure of peroxyl-scavenging capacity, in 1337 members of 40 Mexican American families. TAS levels were significantly lower in women than in men (1.675Ϯ0.004 versus 1.805Ϯ0.005 mmol/L, respectively; PϽ0.001), and there was a significant decline of TAS levels with age in men but not in women (PϽ0.01 for the interaction). Quantitative genetic analysis indicated the heritability of TAS levels to be 0.509Ϯ0.052; ie, Ϸ51% of the residual variance (after covariate adjustment) in TAS levels was due to the additive effects of genes (PϽ0.001). We have further observed a significant gene-by-smoking interaction (PϽ0.05). Additive genetic effects account for 83% of the residual phenotypic variance in TAS levels among smokers, but they account for only 49% in nonsmokers. However, genes contributing to TAS variation are the same in smokers and nonsmokers.

Pediatric metabolic syndrome (MS) and its cardiometabolic components (MSCs) have become increasingly prevalent, yet little is known about the genetics underlying MS risk in children. We examined the prevalence and genetics of MS-related traits among 670 non-diabetic Mexican American (MA) children and adolescents, aged 6–17 years (49 % female), who were participants in the San Antonio Family Assessment of Metabolic Risk Indicators in Youth (SAFARI) study. These children are offspring or biological relatives of adult participants from three well-established Mexican American family studies in San Antonio, Texas, at increased risk of type 2 diabetes. MS was defined as ≥ 3 abnormalities among 6 MSC measures: waist circumference, systolic and/or diastolic blood pressure, fasting insulin, triglycerides, HDL-cholesterol, and fasting and/or 2-h OGTT glucose. Genetic analyses of MS, number of MSCs (MSC-N), MS factors, and bivariate MS traits were performed. Overweight/obesity (53 %), pre-diabetes (13 %), acanthosis nigricans (33 %), and MS (19 %) were strikingly prevalent, as were MS components, including abdominal adiposity (32 %) and low HDL-cholesterol (32 %). Factor analysis of MS traits yielded three constructs: adipo-insulin-lipid, blood pressure, and glucose factors, and their factor scores were highly heritable. MS itself exhibited 68 % heritability. MSC-N showed strong positive genetic correlations with obesity, insulin resistance, inflammation, and acanthosis nigricans, and negative genetic correlation with physical fitness. MS trait pairs exhibited strong genetic and/or environmental correlations. These findings highlight the complex genetic architecture of MS/MSCs in MA children, and underscore the need for early screening and intervention to prevent chronic sequelae in this vulnerable pediatric population.

Our results show that an HCHF diet can directly induce inflammation and endothelial dysfunction. Prior in vivo exposure to an HCHF diet attenuates the in vitro responses of endothelial cells to atherogenic risk factors. This preconditioning phenomenon may have significant clinical relevance.

Abstract-Angiotensin-converting enzyme (ACE) activity is highly heritable and has been associated with cardiovascular disease. We are studying the effects of genes and environmental factors on hypertension and related phenotypes, such as ACE activity, in Mexican-American families. In the current study, we performed multipoint linkage analysis to search for quantitative trait loci (QTLs) that affect ACE activities on data from 793 individuals from 29 pedigrees from the San Antonio Family Heart Study. As expected, we obtained strong evidence (maximum log of the odds [LOD]ϭ4.57, genomic Pϭ0.003) that a QTL for ACE activity is located on chromosome 17 near the ACE structural locus. We subsequently performed linkage analyses conditional on the effect of this QTL and obtained strong evidence (LODϭ3.34) for a second QTL on chromosome 4 near D4S1548. We next incorporated the ACEIns/Del genotypes in our analyses and removed the evidence for the chromosome 17 QTL (maximum LODϭ0.60); however, we retained our evidence for the QTL on chromosome 4q. We conclude that the QTL on chromosome 17 is tightly linked to ACE and is in strong disequilibrium with the insertion/deletion polymorphism, which is consistent with other reports. We also have evidence that an additional QTL affects ACE activity. Identification of this additional QTL might lead to alternate means of prophylaxis. Key Words: ethnic groups Ⅲ blood pressure Ⅲ genetics Ⅲ hypertension, genetic S erum angiotensin-converting enzyme (ACE) activities are highly heritable, and polymorphisms in the ACE structural locus has been reported to account for 19% to 50% of the variation in serum ACE activity. 1 A common Alu repeat insertion/deletion (I/D) in ACE has been associated with increased blood pressure or risk of cardiovascular disease (CVD) in some, but not all, studies. 2 Because the I/D polymorphism resides in an intron, these inconsistent associations might imply that the functional polymorphism is located elsewhere within the ACE locus or even in a nearby gene. Alternatively, these observations might be indicative of the presence of additional genes or genotypeϫenvironment interactions.We are studying genes, environmental factors, and their interactions that influence blood pressure regulation as part of the San Antonio Family Heart Study (SAFHS). In this study, we report the results of our multipoint linkage analyses to detect quantitative trait loci (QTLs) that affect ACE activities and the relation between the I/D polymorphism and the QTLs in a group of large Mexican-American families. Methods SubjectsWe collected systolic and diastolic blood pressure and ACE activity data on 935 Mexican-Americans who had participated in the SAFHS, a population-based, prospective family study of atherosclerosis and its risk factors. 3 Probands (aged 40 to 60 years) for each family were identified from a low-income neighborhood by a house-to-house recruitment procedure. All first-, second-, and thirddegree relatives of each proband and the proband's spouse were invited to participate...