Genetic composition of a Brazilian population: the footprint of the Gold Cycle.

Ancestry-informative markers (AIMs) are powerful tools for inferring the genetic composition of admixed populations. In this study, we determined the genetic ancestry of the Ouro Preto (Brazil) population and evaluated the association between ancestry and self-reported skin color. The genetic ancestry of 189 children and adolescents was estimated by genotyping 15 AIMs. The estimate of population admixture was determined using the Bayesian Markov Chain Monte Carlo (MCMC) method implemented in two different programs (STRUCTURE and ADMIXMAP). Volunteers self-reported their skin colors. The European ancestry contribution ranged from 0.503 to 0.539, the African contribution ranged from 0.333 to 0.425, and the Amerindian component ranged from 0.04 to 0.164. The relative contributions of African (P < 0.016) and European (P < 0.011) ancestry differed significantly among skin color groups, except between black and dark-brown groups. The population of Ouro Preto has a higher contribution of African ancestry compared to the mean for the southeast region of Brazil. Therefore, extrapolating the African ancestry contribution for southeastern Brazil to the Ouro Preto population would underestimate the actual value for this city. We also showed that self-reported skin color could be appropriate for describing the genetic structure of this particular population.

Adiponectin, HOMA-Adiponectin, HOMA-IR in Children and Adolescents: Ouro Preto Study.

OBJECTIVES: To examine the association and predictive capacity of adiponectin levels, HOMA-AD and HOMA-IR indexes with metabolic risk markers in children and adolescents. METHODS: A cross-sectional study was conducted with 691 children and adolescents (7-14 y), of both sexes. Demographic (sex, age), anthropometric (weight, height, body mass index, waist circumference, body fat), biochemical [total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides, fasting glycemia, insulin and adiponectin] and clinical parameters (arterial blood pressure) were analyzed. RESULTS: In multiple linear regression models, metabolic risk were analyzed in relation to adiponectin levels, HOMA-AD and HOMA-IR. ROC curve analysis was used to define the cut-off for metabolic syndrome for each method studied. Adiponectin level was inversely correlated with weight (r = -0.12; p = 0.01), waist circumference (WC) (r = -0.12; p = 0.01), and triglycerides (r = -0.11; p = 0.02); it was directly correlated with HDL (r = 0.10; p = 0.03) only in the adolescents. In the final linear regression model, after adjustment, only triglycerides (p = 0.03) and HDL (p = 0.04) remained significant. However, HOMA-AD and HOMA-IR were associated with metabolic risk and were the most suitable methods for metabolic syndrome screening in both age groups. For children, independent variables explained 16.0% and 14.5% of HOMA-AD and HOMA-IR, respectively. For adolescents, R2 was higher in HOMA-AD and HOMA-IR models (R2adjusted = 31.9% and R2adjusted = 29.6%, respectively). CONCLUSIONS: HOMA-AD and HOMA-IR are better explained by metabolic markers than adiponectin levels.

Apolipoprotein E polymorphism in Brazilian dyslipidemic individuals: Ouro Preto study.

The influence of apolipoprotein E alleles and genotypes on plasma lipid levels was determined in 185 individuals of mixed ethnicity living in Ouro Preto, Brazil. DNA was obtained from blood samples and the genotypes were determined by an RFLP-PCR procedure. The *3 allele was the most frequent (72%), followed by *4 (20%) and *2 (8%); *4 frequency was higher and *2 frequency was lower in the dyslipidemic group than in the normal control group. The *2 carriers presented lower LDL and total cholesterol levels compared to the *3 and *4 carriers. All six expected genotypes were observed in the individuals genotyped: E2/2 (2.1%), E4/4 (2.7%), E2/4 (3.7%), E2/3 (8.0%), E3/3 (53.3%), E3/4 (29.9%); no difference in genotype frequencies was found between the normal and dyslipidemic groups. Compared with *2, the presence of *3 increases more than two times the risk for dyslipidemia (OR = 2.31; P = 0.025; 95% CI = 1.06-5.06) and the presence of *4 increases it three times (OR = 3.31; P = 0.006; 95% CI = 1.36-8.04). The only significant effect of genotype was an increased risk for dyslipidemia in the *4 genotype carriers (E3/4 + E4/4) compared with the *2 genotype carriers (E2/2 + E2/3) with OR = 3.69 (95% CI = 1.25-10.88). The present study indicates that in the Ouro Preto admixed population the presence of APOE *2 can confer a protective effect, whereas the presence of APOE *4 implies an enhanced risk for dyslipidemia.

IGF2, LEPR, POMC, PPARG, and PPARGC1 gene variants are associated with obesity-related risk phenotypes in Brazilian children and adolescents.

Association studies of genetic variants and obesity and/or obesity-related risk factors have yielded contradictory results. The aim of the present study was to determine the possible association of five single-nucleotide polymorphisms (SNPs) located in the IGF2, LEPR, POMC, PPARG, and PPARGC1 genes with obesity or obesity-related risk phenotypes. This case-control study assessed overweight (n=192) and normal-weight (n=211) children and adolescents. The SNPs were analyzed using minisequencing assays, and variables and genotype distributions between the groups were compared using one-way analysis of variance and Pearson's chi-square or Fisher's exact tests. Logistic regression analysis adjusted for age and gender was used to calculate the odds ratios (ORs) for selected phenotype risks in each group. No difference in SNP distribution was observed between groups. In children, POMC rs28932472(C) was associated with lower diastolic blood pressure (P=0.001), higher low-density lipoprotein (LDL) cholesterol (P=0.014), and higher risk in overweight children of altered total cholesterol (OR=7.35, P=0.006). In adolescents, IGF2 rs680(A) was associated with higher glucose (P=0.012) and higher risk in overweight adolescents for altered insulin (OR=10.08, P=0.005) and homeostasis model of insulin resistance (HOMA-IR) (OR=6.34, P=0.010). PPARG rs1801282(G) conferred a higher risk of altered insulin (OR=12.31, P=0.003), and HOMA-IR (OR=7.47, P=0.005) in overweight adolescents. PARGC1 rs8192678(A) was associated with higher triacylglycerols (P=0.005), and LEPR rs1137101(A) was marginally associated with higher LDL cholesterol (P=0.017). LEPR rs1137101(A) conferred higher risk for altered insulin, and HOMA-IR in overweight adolescents. The associations observed in this population suggested increased risk for cardiovascular diseases and/or type 2 diabetes later in life for individuals carrying these alleles.

Choline oxidase chemiluminescent assay, after removal of eserine from medium, of acetylcholine released in vitro from brain slices.

A chemiluminescent method has been used recently for the determination of acetylcholine with limitations such as the presence of a cholinesterase inhibitor in the incubation medium, which is indispensable for the study of acetylcholine release by various agents. A modified procedure is presented in which the cholinesterase inhibitor eserine (physostigmine) is extracted from the medium. The results showed complete recovery when labelled acetylcholine was used. This modified procedure was used to determine the release of acetylcholine evoked by tityustoxin and ouabain. The results were comparable to those obtained by bioassay using a strip of guinea pig ileum.

Relationship between plasma fibrinogen and fiber intake in the EPIC-Norfolk cohort.

BACKGROUND/OBJECTIVES: Fiber-rich diets have been proposed to lower circulating levels of inflammatory makers. Our objective was to investigate cross-sectional relationships between fiber intake and plasma fibrinogen. SUBJECTS/METHODS: We examined the relationship between plasma fibrinogen and dietary fiber in 20,960 men and women, aged 45-75 years old, living in Norfolk, U.K. Fiber intake was assessed using a food frequency questionnaire. RESULTS: Mean fibrinogen levels were lower across the increasing quartiles of the fiber intake after adjusting for age, sex, body mass index, physical activity, smoking status and alcohol consumption, and total calories, percentage of energy intake from carbohydrate, protein and fat, with a difference of 0.08 g/l fibrinogen between first and fourth quartiles (P for trend <0.001) for the whole population. When categorized by sex, the results for men were the same and for women, the results failed to be significant. In linear regression models, fibrinogen levels were significantly related to fiber intake for the whole population (-0.056 g/l, s.e.=0.012 per 10 g increase in fiber intake, P<0.001), but although the relations were in the same direction after adjusting for the same covariates above, they failed to be significant when smokers or women not using post-menopause hormone therapy were separately considered. CONCLUSIONS: Plasma fibrinogen levels appear to be inversely related to dietary fiber intake in middle-aged and older men and women.

Anthropometric methods for obesity screening in schoolchildren: the Ouro Preto Study.

BACKGROUND AND AIMS: Childhood obesity is increasing dramatically in last decades. To evaluate the usefulness of body mass index (BMI), skinfold thickness (ST), waist circumference (WC), and foot-to-foot bioelectrical impedance (BIA-FF) for screening for obesity in mixed-race population, using the tetrapolar bioelectrical impedance (BIA-T) technique as reference method. METHODS AND RESULTS: A cross-sectional-based population study was performed in the city of Ouro Preto, Brazil, in 2006. Schoolchildren aged 6-15 years (n = 788) was randomly selected according to age and sex stratified by the proportion of students in each schools of the city. Nonparametric receiver operating characteristic (ROC) analysis was used to define the sensitivity and specificity for each method studied using the tetrapolar method as reference. The BMI and the BIA-FF were the most suitable for adiposity screening in pre-pubertal and pubertal stages because they present a better balance between sensitivity and specificity, and smaller misclassification. For post-pubertal boys, the BF-ST-D was the best body fat assessment method. CONCLUSION: The results suggest that BIA-FF and BMI are choice methods for obesity screening in mixed population and that the method choice for body fat screening must be done according to sexual maturity of boys and girls. The present study demonstrates the need to perform studies in wider mixed-race population to determine anthropometric parameters and to examine the predictive ability of methods and cut-offs here elucidated in the development of obesity.

IGF2, LEPR, POMC, PPARG, and PPARGC1 gene variants are associated with obesity-related risk phenotypes in Brazilian children and adolescents

Association studies of genetic variants and obesity and/or obesity-related risk factors have yielded contradictory results. The aim of the present study was to determine the possible association of five single-nucleotide polymorphisms (SNPs) located in the IGF2, LEPR, POMC, PPARG, and PPARGC1 genes with obesity or obesity-related risk phenotypes. This case-control study assessed overweight (n=192) and normal-weight (n=211) children and adolescents. The SNPs were analyzed using minisequencing assays, and variables and genotype distributions between the groups were compared using one-way analysis of variance and Pearson's chi-square or Fisher's exact tests. Logistic regression analysis adjusted for age and gender was used to calculate the odds ratios (ORs) for selected phenotype risks in each group. No difference in SNP distribution was observed between groups. In children, POMC rs28932472(C) was associated with lower diastolic blood pressure (P=0.001), higher low-density lipoprotein (LDL) cholesterol (P=0.014), and higher risk in overweight children of altered total cholesterol (OR=7.35, P=0.006). In adolescents, IGF2 rs680(A) was associated with higher glucose (P=0.012) and higher risk in overweight adolescents for altered insulin (OR=10.08, P=0.005) and homeostasis model of insulin resistance (HOMA-IR) (OR=6.34, P=0.010). PPARG rs1801282(G) conferred a higher risk of altered insulin (OR=12.31, P=0.003), and HOMA-IR (OR=7.47, P=0.005) in overweight adolescents. PARGC1 rs8192678(A) was associated with higher triacylglycerols (P=0.005), and LEPR rs1137101(A) was marginally associated with higher LDL cholesterol (P=0.017). LEPR rs1137101(A) conferred higher risk for altered insulin, and HOMA-IR in overweight adolescents. The associations observed in this population suggested increased risk for cardiovascular diseases and/or type 2 diabetes later in life for individuals carrying these alleles.

Bracken (Pteridium aquilinum)-induced DNA adducts in mouse tissues are different from the adduct induced by the activated form of the Bracken carcinogen ptaquiloside.

Following treatment with bracken fern (Pteridium aquilinum) extract and bracken spores a number of DNA adducts were detected by (32)P-postlabeling. Three of these adducts have been described previously (Povey et al., Br. J. Cancer (1996) 74, 1342-1348) and in this study, using a slightly different protocol, four new adducts, with higher chromatographic mobility, were detected at levels ranging from 50 to 230% of those previously described. When DNA was treated in vitro with activated ptaquiloside (APT) and analysed by butanol extraction or nuclease P1 treatment, only one adduct was detected by (32)P-postlabeling. This adduct was not present in the DNA from mice treated with bracken fern or spores, suggesting either that bracken contains genotoxins other than ptaquiloside or that the metabolism of ptaquiloside produces genotoxins not reflected by activated ptaquiloside. However, as the ATP-derived adduct has been detected previously in ileal DNA of bracken-fed calves, species-specific differences in the metabolism of bracken genotoxins may exist, thereby leading to differences in their biological outcomes.

Apolipoprotein E polymorphism in Brazilian dyslipidemic individuals: Ouro Preto study

The influence of apolipoprotein E alleles and genotypes on plasma lipid levels was determined in 185 individuals of mixed ethnicity living in Ouro Preto, Brazil. DNA was obtained from blood samples and the genotypes were determined by an RFLP-PCR procedure. The *3 allele was the most frequent (72 percent), followed by *4 (20 percent) and *2 (8 percent); *4 frequency was higher and *2 frequency was lower in the dyslipidemic group than in the normal control group. The *2 carriers presented lower LDL and total cholesterol levels compared to the *3 and *4 carriers. All six expected genotypes were observed in the individuals genotyped: E2/2 (2.1 percent), E4/4 (2.7 percent), E2/4 (3.7 percent), E2/3 (8.0 percent), E3/3 (53.3 percent), E3/4 (29.9 percent); no difference in genotype frequencies was found between the normal and dyslipidemic groups. Compared with *2, the presence of *3 increases more than two times the risk for dyslipidemia (OR = 2.31; P = 0.025; 95 percent CI = 1.06-5.06) and the presence of *4 increases it three times (OR = 3.31; P = 0.006; 95 percent CI = 1.36-8.04). The only significant effect of genotype was an increased risk for dyslipidemia in the *4 genotype carriers (E3/4 + E4/4) compared with the *2 genotype carriers (E2/2 + E2/3) with OR = 3.69 (95 percent CI = 1.25-10.88). The present study indicates that in the Ouro Preto admixed population the presence of APOE *2 can confer a protective effect, whereas the presence of APOE *4 implies an enhanced risk for dyslipidemia.