IL1RN genetic variations and risk of IPF: a meta-analysis and mRNA expression study

Idiopathic pulmonary fibrosis (IPF) is a rare and devastating lung disease of unknown aetiology. Genetic variations in the IL1RN gene, encoding the interleukin-1 receptor antagonist (IL-1Ra), have been associated with IPF susceptibility. Several studies investigated the variable number tandem repeat (VNTR) or single nucleotide polymorphisms rs408392, rs419598 and rs2637988, with variable results. The aim of this study was to elucidate the influence of polymorphisms in IL1RN on IPF susceptibility and mRNA expression. We performed a meta-analysis of the five case–control studies that investigated an IL1RN polymorphism in IPF in a Caucasian population. In addition, we investigated whether IL1RN mRNA expression was influenced by IL1RN polymorphisms. The VNTR, rs408392 and rs419598 were in tight linkage disequilibrium, with D′ > 0.99. Furthermore, rs2637988 was in linkage disequilibrium with the VNTR (D′ = 0.90). A haploblock of VNTR*2 and the minor alleles of rs408392and rs419598 was constructed. Meta-analysis revealed that this VNTR*2 haploblock is associated with IPF susceptibility both with an allelic model (odds ratio = 1.42, p = 0.002) and a carriership model (odds ratio = 1.60, p = 0.002). IL1RN mRNA expression was significantly influenced by rs2637988, with lower levels found in carriers of the (minor) GG genotype (p < 0.001). From this meta-analysis, we conclude that the VNTR*2 haploblock is associated with susceptibility to IPF. In addition, polymorphisms in IL1RN influence IL-1Ra mRNA expression, suggesting that lower levels of IL-1Ra predispose to developing IPF. Together these findings demonstrate that the cytokine IL-1Ra plays a role in IPF pathogenesis

Association between Variations in Cell Cycle Genes and Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a devastating and progressive lung disease. Its aetiology is thought to involve damage to the epithelium and abnormal repair. Alveolar epithelial cells near areas of remodelling show an increased expression of proapoptotic molecules. Therefore, we investigated the role of genes involved in cell cycle control in IPF. Genotypes for five single nucleotide polymorphisms (SNPs) in the tumour protein 53 (TP53) gene and four SNPs in cyclin-dependent kinase inhibitor 1A (CDKN1A), the gene encoding p21, were determined in 77 IPF patients and 353 controls. In peripheral blood mononuclear cells (PBMC) from 16 healthy controls mRNA expression of TP53 and CDKN1A was determined

A General Approach To Modelling Non-normally Distributed Cost Variance Data: An Illustration

Many studies have indicated that many financial and cost variables are non-normally distributed. For example, empirical studies of financial ratios and cost variance data have found non-normality. However, instead of identifying the correct distribution of these financial variables, many of these decision models (e.g. bankruptcy prediction, bond rating prediction, cost-volume-profit analysis and the cost variance investigation decision) have simply adopted an assumption of normality. This is contrary to the empirical evidence which has suggested that some of these input variables are non-normally distributed. The reason for this common adoption of the normal distribution assumption could be attributed to the lack of knowledge regarding the appropriate distribution function for the variable. In order to encourage the use of the appropriate distribution function for the required financial variable, this paper examines this aspect. The objective of this study is to assist in identifying an appropriate distribution function for modelling non-normally distributed accounting variables. A three-step procedure is described and actual cost variance data of a Fortune 500 company's manufacturing plant are used to illustrate the procedure. © 1993 Academic Press. All rights reserved.link_to_subscribed_fulltex

Native-valve endocarditis caused by Staphylococcus lugdunensis.

Coagulase-negative staphylococci cause about 5% of native-valve endocarditis. Staphylococcus lugdunensis, a recently-described species of coagulase-negative staphylococci, has been reported to cause destructive native-valve endocarditis with a high mortality. We report four consecutive cases of definite Staphylococcus lugdunensis native-valve endocarditis by the Duke criteria over a 4-year period. All patients required urgent aortic valve replacement 1-5 days after admission, and recovered. An intriguing, aspect in the presentation of these patients was a history of vasectomy and inguinal skin breaks in the immediate period preceding the occurrence of endocarditis