Protective effect of the APOE-e3 allele in Alzheimer’s disease

Although several alleles of susceptibility to Alzheimer’s disease (AD) have been studied in the last decades, few polymorphisms have been considered as risk factors for the disease. Among them, the APOE-e4 allele appears to be the major genetic risk factor for the onset of the disease. However, it is important to confirm the potential susceptibility of these genetic variants in different populations in order to establish a genetic profile for the disease in specific communities. This study analyzed the APOE polymorphisms regarding susceptibility to AD in a sample of 264 individuals (primarily Caucasians; 82 cases and 182 controls) in the population from Vitória, ES, Brazil, by PCR restriction fragment length polymorphism (PCR-RFLP) methods. The patients were selected according to clinical criteria for probable AD. Whereas the e4 allele showed statistically significant positive association with susceptibility to AD (OR = 3.01, 95 percentCI = 1.96-4.61; P < 0.0001), the e2 allele did not. The results of the e4 allele confirm the role of this polymorphism as a risk factor for AD in the sample studied as observed in other populations. Although the e3 allele has been considered neutral in several studies, our results suggest that it acts as a protective factor against AD in the population studied (OR = 0.46, 95 percentCI = 0.30-0.67; P < 0.0001). This study may provide a new insight into the role of the APOE-e3 allele in the etiology of AD and might help to estabilish a profile of risk for AD in the population from Vitória, ES.

Molecular cytogenetic analysis of a ring-Y infertile male patient

In the present study, we report on the case of a 43-year-old male patient seeking for fertility assistance, who showed a seminal analysis and testicular biopsy of complete azoospermia. Peripheral blood culture for chromosome studies revealed a karyotype of 46 chromosomes with a ring-Y-chromosome that lost the long arm heterochromatin. Molecular analysis of genomic DNA from the patient detected the presence of the sex-determining region of the Y-chromosome (SRY) but the complete absence of regions involved in spermatogenesis (AZFa, AZFb, AZFc). Several molecular markers distributed along the Y-chromosome were tested through PCR amplification, and a breakpoint was established close to the centromere, predicting the deletion of the growth control region, in agreement with the short stature observed in this patient. All results obtained through molecular cytogenetic characterization are in accordance with the clinical features observed in this patient.

Oncogene-induced transcriptional patterns in established cell lines as a model for in vitro analysis of tumor biology

Established cell lines have long been used for in vitro studies of tumor biology, enabling investigators to control growth conditions and to draw important conclusions about the oncogenic microenvironment. However, gene expression behavior in cultured cells may not always reflect the actual in vivo scenario, and analysis derived from such experiments should take into consideration the existing differences between the two environments. We used suppression subtractive hybridization to study transcriptional changes elicited after oncogene transformation and cell line establishment. We found that transcriptional changes elicited in cultured cell lines are in fact representative of late events, and they do not occur early after oncogene transfection or activation. We also determined that a fraction of the transcriptional changes is oncogene specific, whereas other changes are shared between two or more different oncogenes.