Performance evaluation of biochemical and ultrasound markers for the screening of chromosomal numerical abnormalities in the first trimester of pregnancy.

BACKGROUND: To estimate the effectiveness of the first-trimester combined screening test in our population, departing from the results of diagnostic sensitivity and false positive rate (FPR), and checking some important parameters in prenatal screening. METHODS: The test was evaluated on 14250 pregnant women. The following variables were studied: the number of invasive techniques and the reasons for using such techniques, newborns with chromosomal abnormalities, total number of births, variation of biochemical markers throughout the gestational weeks, and MoM (multiple of the median) for biochemical and ultrasound markers. RESULTS: An important coverage and a decreased number of invasive techniques were obtained. For our population of pregnant women, the best gestational week to determine free beta-hCG and PAPP-A would be week 11 in which the best discrimination was found between affected and non affected fetuses for the three trisomies researched. We propose the cut-off 1/350, because it is the best one to increase sensitivity without exceeding the 5% FPR. CONCLUSIONS: Combined screening should be offered to pregnant woman, preferentially at week 11. Although different cut-offs for this prenatal test have been recommended by scientific societies, biochemical laboratories should set their own cut-off for getting the best sensitivity and FPR results. There should be a good level of collaboration between the laboratory and each participating ultrasound unit in order to ensure an optimal use of the first-trimester combined screening test.

Association study and meta-analysis of Alzheimer's disease risk and presenilin-1 intronic polymorphism.

Numerous studies have tested for associations between an intronic polymorphism (rs165932) of presenilin-1 (PS-1) gene and the risk of Alzheimer's disease (AD), but results have been conflicting. To throw light on this issue, we investigate the possible involvement of PS-1 genotype in a case-control study based on a relatively stable population in Spain and a meta-analysis of published studies. An examination was conducted of 85 patients with probable or possible AD, along with controls from the same community, by using an chi(2) test for homogeneity and a binary logistic regression model. For comparison purposes, a meta-analysis of data from all available published studies was assessed. In our patients, homozygosity of the allele 2 in the PS-1 gene increased for late-onset AD (OR 2.38, 95% CI 1.07-5.29, P<0.05). The presence of at least one allele of apoE was also associated with AD (OR 4.01, 95% CI 1.93-8.34, p<0.05). The regression model showed that, overall, the presence of the apoE epsilon 4 allele and the PS-1 2/2 genotype were independent factors for the development of AD in our sample. In our genotype-based meta-analysis, the PS-1 2/2 genotype was probably related with AD for the European sub-group (fixed effects model, OR 1.19, 95% CI 1.02-1.37, p<0.05), but there are many confusing factors between different studies. Presenilin-1 2/2 genotype is a risk factor for late onset Alzheimer disease in the Spanish population, and probably, for Europeans.

Real time PCR assay with fluorescent hybridization probes for genotyping intronic polymorphism in presenilin-1 gene.

BACKGROUND: Identification of all susceptibility loci for Alzheimer's disease has been a major goal in resolving the pathogenesis of this disease. METHODS: A PCR assay with fluorescently labeled oligonucleotide hybrinization probes with subsequent fluorescent probe melting point analysis was developed. RESULTS: Allelic discrimination of intronic polymorphism of presenilin-1 gene and the restriction fragment length polymorphism method yielded identical results, proving its usefulness for genotyping PS1 gene. CONCLUSIONS: This method provides excellent robustness, speed, and accuracy, and is well suited for determination of the polymorphism in both small and large numbers of samples. This assay could help to overcome the controversy regarding the association between the PS1 s165932 intronic polymorphism and Alzheimer's disease.