Predictive value of common genetic variants in idiopathic pulmonary fibrosis survival.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial pneumonia of unknown etiology. The role of genetic risk factors has been the focus of numerous studies probing for associations of genetic variants with IPF. We aimed to determine whether single-nucleotide polymorphisms (SNPs) of four candidate genes are associated with IPF susceptibility and survival in a Portuguese population. A retrospective case-control study was performed with 64 IPF patients and 74 healthy controls. Ten single-nucleotide variants residing in the MUC5B, TOLLIP, SERPINB1, and PLAU genes were analyzed. Single- and multi-locus analyses were performed to investigate the predictive potential of specific variants in IPF susceptibility and survival. Multifactor dimensionality reduction (MDR) was employed to uncover predictive multi-locus interactions underlying IPF susceptibility. The MUC5B rs35705950 SNP was significantly associated with IPF: T allele carriers were significantly more frequent among IPF patients (75.0% vs 20.3%, P < 1.0 × 10-6). Genotypic and allelic distributions of TOLLIP, PLAU, and SERPINB1 SNPs did not differ significantly between groups. However, the MUC5B-TOLLIP T-C-T-C haplotype, defined by the rs35705950-rs111521887-rs5743894-rs5743854 block, emerged as an independent protective factor in IPF survival (HR = 0.37, 95% CI 0.17-0.78, P = 0.009, after adjustment for FVC). No significant multi-locus interactions correlating with disease susceptibility were detected. MUC5B rs35705950 was linked to an increased risk for IPF, as reported for other populations, but not to disease survival. A haplotype incorporating SNPs of the MUC5B-TOLLIP locus at 11p15.5 seems to predict better survival and could prove useful for prognostic purposes and IPF patient stratification. KEY MESSAGES : The MUC5B rs35705950 minor allele is associated with IPF risk in the Portuguese. No predictive multi-locus interactions of IPF susceptibility were identified by MDR. A haplotype defined by MUC5B and TOLLIP SNPs is a protective factor in IPF survival. The haplotype may be used as a prognostic tool for IPF patient stratification.

[Bone marrow volunteer donors recruitment in northern Portugal]. / Recrutamento de dadores voluntários de medula óssea no norte de Portugal.

Allogeneic haematopoietic stem cell transplantation (HSCT) has been used to treat a variety of malignant and non-malignant diseases, particularly of the blood and immune system. However, as no more than 30% of patients will have HLA-identical sibling, much effort has been devoted to the establishment of bone marrow registries for HSCT. In 2010, there are more than 15 million bone marrow donors and cord blood units in the in the Bone Marrow Donors Worldwide (BMDW) database. Participants are 64 stem cell donor registries from 44 countries, and 44 cord blood banks from 26 countries. The North Center of Histocompatibility (CHN) is one of the three Histocompatibility Centers which made the Portuguese Registry of bone marrow donors--National Center of Bone Marrow, Stem Cells and Cord Blood Donors (CEDACE). The aim of this paper is to present the first 110000 donors recruited by the CHN to the CEDACE. In 2010, the recruited donors throw the CHN distribution by age are 14.6%, 38.7%, 37.8% and 8.9%, for the age groups [18;25], [25;35], [35;45] and = 45, respectively. The 110000 bone marrow donors recruited in the North of Portugal by the CHN are a contribution to the worldwide effort that is the BMDW. Young, preferably male donors, should be targeted as replacement of the donors who retire because of old age or for other reasons. Also, the quest for donors with the so-called unique phenotypes is a challenge for all registries. Portuguese areas which show particularly high levels of phenotype diversity or those in which alleles of haplotypes underrepresented in the registry are identified can and should be targeted for the optimization of recruitment strategies.