Testing for the association of the KIAA1109/Tenr/IL2/IL21 gene region with rheumatoid arthritis in a European family-based study

INTRODUCTION: A candidate gene approach, in a large case-control association study in the Dutch population, has shown that a 480 kb block on chromosome 4q27 encompassing KIAA1109/Tenr/IL2/IL21 genes is associated with rheumatoid arthritis. Compared with case-control association studies, family-based studies have the added advantage of controlling potential differences in population structure. Therefore, our aim was to test this association in populations of European origin by using a family-based approach. METHODS: A total of 1,302 West European white individuals from 434 trio families were genotyped for the rs4505848, rs11732095, rs6822844, rs4492018 and rs1398553 polymorphisms using the TaqMan Allelic discrimination assay (Applied Biosystems). The genetic association analyses for each SNP and haplotype were performed using the Transmission Disequilibrium Test and the genotype relative risk. RESULTS: We observed evidence for association of the heterozygous rs4505848-AG genotype with rheumatoid arthritis (P = 0.04); however, no significance was found after Bonferroni correction. In concordance with previous findings in the Dutch population, we observed a trend of undertransmission for the rs6822844-T allele and rs6822844-GT genotype to rheumatoid arthritis patients. We further investigated the five SNP haplotypes of the KIAA1109/Tenr/IL2/IL21 gene region. We observed, as described in the Dutch population, a nonsignificant undertransmission of the AATGG haplotype to rheumatoid arthritis patients. CONCLUSIONS: Using a family-based study, we have provided a trend for the association of the KIAA1109/Tenr/IL2/IL21 gene region with rheumatoid arthritis in populations of European descent. Nevertheless, we failed to replicate a significant association of this region in our rheumatoid arthritis family sample. Further investigation of this region, including detection and testing of all variants, is required to confirm rheumatoid arthritis association

The ITGAV rs3738919-C allele is associated with rheumatoid arthritis in the European Caucasian population: a family-based study

The integrin αvβ3, whose αv subunit is encoded by the ITGAV gene, plays a key role in angiogenesis. Hyperangiogenesis is involved in rheumatoid arthritis (RA) and the ITGAV gene is located in 2q31, one of the suggested RA susceptibility loci. Our aim was to test the ITGAV gene for association and linkage to RA in a family-based study from the European Caucasian population

Bactericidal and virucidal activity of the alkalophilic P395D/L241V/T343A mutant of vanadium chloroperoxidase

Aims: Vanadium chloroperoxidase and its directed evolution mutant P395D/L241V/T343A were investigated for their antibacterial and antiviral potential at slightly alkaline pH and at a H2O2 concentration that is low compared to current nonenzymatic formulations. Methods and Results: Two bacteria (the Gram-negative Pseudomonas aeruginosa and the Gram-positive Staphylococcus aureus) and two viruses (the enveloped Herpes Simplex Virus and the nonenveloped Coxsackievirus B4) were incubated with the P395D/L241V/T343A mutant, 10 mmol l(-1) H2O2 and 100 mmol l(-1) Br- at pH 8. Strong microbial reduction was observed and bactericidal and virucidal activities of the mutant were three to six orders of magnitude higher than for the wild-type enzyme. Conclusions: The P395D/L241V/T343A mutant of vanadium chloroperoxidase has a broad antimicrobial activity at alkaline conditions. Significance and Impact of the Study: For many disinfection formulations, antimicrobial activity at slightly alkaline pH values is required. To date, only the wild-type vanadium chloroperoxidase has been studied for its antibacterial activity, and only at acidic to neutral pH values. Its antiviral activity (e.g. useful for the cleaning of medical equipment) was not studied before. The observed activity for the alkalophilic P395D/L241V/T343A mutant is an important step forward in the application of this robust enzyme as a component in disinfection formulations

Optimisation of the chemical generation of singlet oxygen (¹Ο₂, ¹Δ_g) from the hydrogen peroxide–lanthanum(III) catalytic system using an improved NIR spectrometer

A near-IR chemiluminescence spectrometer designed to study chemical sources of singlet oxygen (1Ο2, 1Δg), was built by coupling a reactor compartment to a nitrogen-cooled Ge diode through a bundle of optical fibres. This device was used to optimise the generation of 1O2 from the hydrogen peroxide–lanthanum(III) catalytic system. The reaction kinetics were studied with a 2333//12 screening experimental design comprising twelve experiments. The influence of six factors was examined: the nature of the lanthanum salt (hydroxide, oxide or nitrate) and its concentration (0.05 or 0.1 mol L-1), the pH value (5, 7 or 9), the concentration of H2O2 (0.5, 1 or 2 mol L-1), the temperature (20 or 30 °C) and the concentration of EDTA (0 or 5 mmol L-1). Two responses were measured: the rate of H2O2 disproportionation and the intensity of the luminescence of 1O2 at 1270 nm. The essential factor is the nature of the lanthanum salt since La(NO3)3 induces the disproportionation of H2O2 about 60 × faster than La2O3 or La(OH)3. Other influencing factors are the pH value, the concentration of H2O2, the temperature and the concentration of the lanthanum salt whereas the concentration of EDTA has no effect on the reaction. The catalytic activity of La(NO3)3 was then investigated in further detail by studying the influence of two factors (pH and [H2O2]) thanks to a Doehlert design