Risk factors, biochemical markers, and genetic polymorphisms in early coronary artery disease

OBJECTIVE: To assess the risk factors, lipid and apolipoprotein profile, hemostasis variables, and polymorphisms of the apolipoprotein AI-CIII gene in early coronary artery disease (CAD). METHODS: Case-control study with 112 patients in each group controlled by sex and age. After clinical evaluation and nutritional instruction, blood samples were collected for biochemical assays and genetic study. RESULTS: Familial history of early CAD (64 vs 39%), arterial hypertension (69 vs 36%), diabetes mellitus (25 vs 3%), and previous smoking (71 vs 46%) were more prevalent in the case group (p<0.001). Hypertension and diabetes were independent risk factors. Early CAD was characterized by higher serum levels of total cholesterol (235 ± 6 vs 209 ± 4 mg/dL), of LDL-c (154 ± 5 vs 135 ± 4 mg/dL), triglycerides (205 ± 12 vs 143 ± 9 mg/dL), and apolipoprotein B (129 ± 3 vs 105 ± 3 mg/dL), and lower serum levels of HDL-c (40 ± 1 vs 46 ± 1 mg/dL) and apolipoprotein AI (134 ± 2 vs 146 ± 2mg/dL) [p<0.01], in addition to an elevation in fibrinogen and D-dimer (p<0.02). The simultaneous presence of the rare alleles of the APO AI-CIII genes in early CAD are associated with hypertriglyceridemia (p=0.03). CONCLUSION: Of the classical risk factors, hypertension and diabetes mellitus were independently associated with early CAD. In addition to an unfavorable lipid profile, an increase in the thrombotic risk was identified in this population. An additive effect of the APO AI-CIII genes was observed in triglyceride levels.

Genetic and Environmental Effects on the Abdominal Aortic Diameter Development

Abstract Background: Configuration of the abdominal aorta is related to healthy aging and a variety of disorders. Objectives: We aimed to assess heritable and environmental effects on the abdominal aortic diameter. Methods: 114 adult (69 monozygotic, 45 same-sex dizygotic) twin pairs (mean age 43.6 ± 16.3 years) underwent abdominal ultrasound with Esaote MyLab 70X ultrasound machine to visualize the abdominal aorta below the level of the origin of the renal arteries and 1-3 cm above the bifurcation. Results: Age- and sex-adjusted heritability of the abdominal aortic diameter below the level of the origin of the renal arteries was 40% [95% confidence interval (CI), 14 to 67%] and 55% above the aortic bifurcation (95% CI, 45 to 70%). None of the aortic diameters showed common environmental effects, but unshared environmental effects were responsible for 60% and 45% of the traits, respectively. Conclusions: Our analysis documents the moderate heritability and its segment-specific difference of the abdominal aortic diameter. The moderate part of variance was explained by unshared environmental components, emphasizing the importance of lifestyle factors in primary prevention. Further studies in this field may guide future gene-mapping efforts and investigate specific lifestyle factors to prevent abdominal aortic dilatation and its complications.

Morphometric and genetic differentiation among populations of Eupemphix nattereri (Amphibia, Anura, Leiuperidae) from central Brazil

To assess genetic structure and phenotypic diversity of Eupemphix nattereri Steindachner, 1863, morphometric and molecular analyses were carried out for nine populations from the State of Goiás. A total of 11 morphometric traits were evaluated and genetic information was estimated using RAPD markers. Genetic and phenotypic distances were determined as a function of geographical origin. Correlation among genetic, morphometric, micro, and macroenviromental were analyzed by the Mantel test. Genetic data indicated high levels of genetic diversity (Φst= 0.3) among the nine populations. Mantel tests did not reveal a significant positive correlation between genetic and geographical distances, indicating that locally geographical populations were not genetically similar, even in distances smaller than 50 km. Discriminant analysis on 11 morphometric measurements showed a high divergence among the nine populations. However, a marginally significant correlation (P=0.08) between genetic and morphometric distances was found. The observed correlation was not causal in terms of the relationship between phenotype and genotype, but indicated common spatial structures. Thus, our results suggest that isolation-by-distance processes may explain population divergence in Eupemphix nattereri.

Genetic complementation analysis of two independently isolated hycanthone-resistant strains of Schistosoma mansoni

The objective of this study is to determine whether various hycanthone resistant strains of schistosomes which have been independently isolated are all affected in the same gene. A strain obtained from a Brazilian patient was compared with a strain of Puerto Rican origin selected in the laboratory. If the mutation conferring resistance involved two different genes, one would expect that the progeny of a cross between the two strains would show complementation, i.e. it would be sensitive to the drug. We have performed such a cross and obtained F1 hybrid worms wich were essentially all resistant, thus suggesting that the mutation conferring resistance in the two strains involves the same gene.

A molecular genetic study of the variations in metabolic function during schistosome development

During their complex life cycle schistosomes alternate between the use of stored glycogen and reliance on host glucose to provide for their energy needs. In addition, there is dramatic variation between the relative contribution of aerobic versus anaerobic glucose metabolism during development. We have cloned a set of representative cDNAs that encode proteins involved in glucose uptake, glycolysis, Kreb's cycle and oxidative phosphorylation. The different cDNAs were used as probes to examine the expression of glucose metabolism genes during the schistosome life cycle. Steady state mRNA levels from whole cercariae, isolated cercarial tails, schistosomula and adult worms were analysed on Northern blots and dot blots which were quantified using storage phosphor technology. These studies reveal: (1) Transcripts encoding glycogen metabolic enzymes are expressed to much higher levels in cercarial tails than whole cercariae or schistosomula while the opposite pattern is found for glucose transporters and hexokinase transcripts; (2) Schistosomula contain low levels of transcripts encoding respiratory enzymes but regain the capacity for aerobic glucose metabolism as they mature to adulthood; (3) Male and female adults contain similar levels of the different transcripts involved in glucose metabolism.

Genetic variability and differentiation between populations of Rhodnius prolixus and R. pallescens, vectors of Chagas' Disease in Colombia

Enzyme polymorphism in Rhodnius prolixus and R. pallescens (Hemiptera, Reduviidae), principal vectors of Chagas' disease in Colombia, was analyzed using starch gel electrophoresis. Three geographic locations were sampled in order to determine gene flow between populations and to characterize intra- and interspecific differences. Of 25 enzymes assayed 10 were successfully resolved and then used to score the genetic variation. The enzymes PEPD, GPI, PGM and ICD were useful to differentiate these species and PGD, PGM and MDH distinguished between sylvatic and domiciliary populations of R. prolixus. Both polymorphism and heterozygosity indicated greater genetic variability in sylvatic habitats (H = 0.021) compared to domiciliary habitats (H = 0.006) in both species. Gene flow between sylvatic and domiciliary populations in R. prolixus was found to be minimal. This fact and the genetic distance between them suggest a process of genetic isolation in the domiciliary population.

A possible correlation between the host genetic background in the epidemiology of Hepatitis B virus in the Amazon region of Brazil

The Amazon region of Brazil is an area of great interest because of the large distribution of hepatitis B virus in specific Western areas. Seven urban communities and 24 Indian groups were visited in a total of 4,244 persons. Each individual was interviewed in order to obtain demographic and familial information. Whole blood was collected for serology and genetic determinations. Eleven genetic markers and three HBV markers were tested. Among the most relevant results it was possible to show that (i) there was a large variation of previous exposure to HBV in both urban and non-urban groups ranging from 0 to 59.2%; (ii) there was a different pattern of epidemiological distribution of HBV that was present even among a same linguistic Indian group, with mixed patterns of correlation between HBsAg and anti-HBs and (iii) the prevalence of HBV markers (HBsAg and anti-HBs) were significantly higher (P=0.0001) among the Indian population (18.8%) than the urban groups (12.5%). Its possible that the host genetic background could influence and modulate the replication of the virus in order to generate HB carrier state.

Dried blood spots collected on filter paper: an international resource for the diagnosis and genetic characterization of human immunodeficiency virus Type-1

The collection of dried blood spots (DBS) on filter paper provides a powerful approach for the development of large-scale, population-based screening programs. DBS methods are particularly valuable in developing countries and isolated rural regions where resources are limited. Large numbers of field specimens can be economically collected and shipped to centralized reference laboratories for genetic and (or) serological analysis. Alternatively, the dried blood can be stored and used as an archival resource to rapidly establish the frequency and distribution of newly recognized mutations, confirm patient identity or track the origins and emergence of newly identified pathogens. In this report, we describe how PCR-based technologies are beginning to interface with international screening programmes for the diagnosis and genetic characterization of human immunodeficiency virus type 1 (HIV-1). In particular, we review recent progress using DBS specimens to resolve the HIV-1 infection status of neonates, monitor the genetic evolution of HIV-1 during early infancy and establish a sentinel surveillance system for the systematic monitoring of HIV-1 genetic variation in Asia.