Associação independente da variante rs1333049, no locus 9p21, com a doença coronária, numa população portuguesa

Funding: This study was supported by the European Regional Development Fund’s Operational Programme for the Enhancement of Economic Potential and Territorial Cohesion for the Autonomous Region of Madeira (INTERVIR+).Introduction: Recent genome-wide association studies have identified single-nucleotide polymorphisms (SNPs) at the 9p21 locus as risk factors for coronary artery disease (CAD). Among them, the SNP rs1333049 has demonstrated a consistent association with CAD, which has been successfully replicated in several populations. Aim: To investigate whether the SNP rsl333049 located on the 9p21 chromosome is an independent risk factor for CAD in a Portuguese population. Methods: We performed a case-control study which included 1406 individuals, 723 consecutive coronary patients (mean age 53.7±8.9 years, 79.9% male) and 683 controls without coronary disease (mean age 53.3±10.5 years, 73.9% male). Cases and controls were selected so as not to be significantly different in terms of gender and age. We studied the SNP rs1333049 at the 9p21 locus in all individuals, using standard PCR combined with the TaqMan technique (Applied Biosystems). The allelic and genotype distribution (C/G), odds ratios and corresponding confidence intervals for CAD risk were determined. A forward Wald logistic regression analysis model was constructed, adjusted for age, gender, conventional risk factors, biochemical markers and the genotypes under study, in order to determine which variables were linked significantly and independently with CAD. Results: The C allele was found in 60% of the CAD patients and 53% of the controls, with OR=1.33; p=0.0002. The CC genotype appeared in 35.7% of CAD patients, with OR=1.34, p=0.010. The heterozygous CG genotype was present in 48.1% of the CAD patients and 47% of the controls, and did not present vascular risk (OR=1.05, p=0.670). After logistic regression analysis, the CC genotype remained in the equation with 0R=1.7; p=0.018 and CG with OR=I.5, p=0.048. Conclusion: In the present study we replicated the coronary risk linked to the recently discovered variant rs1333049 on the 9p21 chromosome in a Portuguese population. Although the mechanism underlying the risk is still unknown, the robustness of this risk allele in risk stratification for CAD has been consistent, even in very different populations. The presence of the CC or CG genotype may thus prove to be useful for predicting the risk of developing CAD in the Portuguese population.publishersversionpublishe

Limits on spin-dependent WIMP-nucleon cross-sections from the first ZEPLIN-II data

The first underground data run of the ZEPLIN-II experiment has set a limit on the nuclear recoil rate in the two-phase xenon detector for direct dark matter searches. In this paper the results from this run are converted into the limits on spin-dependent WIMP-proton and WIMP-neutron cross-sections. The minimum of the curve for WIMP-neutron cross-section corresponds to 0.07 pb at a WIMP mass of around 65 GeV.Comment: 12 pages, 2 figures, to be published in Physics Letters

The ZEPLIN-III dark matter detector: performance study using an end-to-end simulation tool

We present results from a GEANT4-based Monte Carlo tool for end-to-end simulations of the ZEPLIN-III dark matter experiment. ZEPLIN-III is a two-phase detector which measures both the scintillation light and the ionisation charge generated in liquid xenon by interacting particles and radiation. The software models the instrument response to radioactive backgrounds and calibration sources, including the generation, ray-tracing and detection of the primary and secondary scintillations in liquid and gaseous xenon, and subsequent processing by data acquisition electronics. A flexible user interface allows easy modification of detector parameters at run time. Realistic datasets can be produced to help with data analysis, an example of which is the position reconstruction algorithm developed from simulated data. We present a range of simulation results confirming the original design sensitivity of a few times $10^{-8}$ pb to the WIMP-nucleon cross-section.Comment: Submitted to Astroparticle Physic