Polymorphisms in the tyrosine kinase 2 and interferon regulatory factor 5 genes are associated with systemic lupus erythematosus

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldSystemic lupus erythematosus (SLE) is a complex systemic autoimmune disease caused by both genetic and environmental factors. Genome scans in families with SLE point to multiple potential chromosomal regions that harbor SLE susceptibility genes, and association studies in different populations have suggested several susceptibility alleles for SLE. Increased production of type I interferon (IFN) and expression of IFN-inducible genes is commonly observed in SLE and may be pivotal in the molecular pathogenesis of the disease. We analyzed 44 single-nucleotide polymorphisms (SNPs) in 13 genes from the type I IFN pathway in 679 Swedish, Finnish, and Icelandic patients with SLE, in 798 unaffected family members, and in 438 unrelated control individuals for joint linkage and association with SLE. In two of the genes--the tyrosine kinase 2 (TYK2) and IFN regulatory factor 5 (IRF5) genes--we identified SNPs that displayed strong signals in joint analysis of linkage and association (unadjusted P<10(-7)) with SLE. TYK2 binds to the type I IFN receptor complex and IRF5 is a regulator of type I IFN gene expression. Thus, our results support a disease mechanism in SLE that involves key components of the type I IFN system

A candidate gene study of the type I interferon pathway implicates IKBKE and IL8 as risk loci for SLE

Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease in which the type I interferon pathway has a crucial role. We have previously shown that three genes in this pathway, IRF5, TYK2 and STAT4, are strongly associated with risk for SLE. Here, we investigated 78 genes involved in the type I interferon pathway to identify additional SLE susceptibility loci. First, we genotyped 896 single-nucleotide polymorphisms in these 78 genes and 14 other candidate genes in 482 Swedish SLE patients and 536 controls. Genes with P<0.01 in the initial screen were then followed up in 344 additional Swedish patients and 1299 controls. SNPs in the IKBKE, TANK, STAT1, IL8 and TRAF6 genes gave nominal signals of association with SLE in this extended Swedish cohort. To replicate these findings we extracted data from a genomewide association study on SLE performed in a US cohort. Combined analysis of the Swedish and US data, comprising a total of 2136 cases and 9694 controls, implicates IKBKE and IL8 as SLE susceptibility loci (Pmeta=0.00010 and Pmeta=0.00040, respectively). STAT1 was also associated with SLE in this cohort (Pmeta=3.3 × 10−5), but this association signal appears to be dependent of that previously reported for the neighbouring STAT4 gene. Our study suggests additional genes from the type I interferon system in SLE, and highlights genes in this pathway for further functional analysis

Pressure build-up in geothermal re-injection wells

This paper presents a case study of pressure build-up in some geothermal re-injection wells in Sweden. The geothermal heat plant, in which the re-injection wells are used, has been in operation since the beginning of 1985. Each day since the start of the geothermal plant registration of the injection pressure has been done. The paper describes how a stimulation of the gravel pack outside the well screen can improve the hydraulic performance of the well. The stimulation is done by reversing the flow direction in the well. It is also shown how important it is to have a good well completion in order to receive a positive effect of well stimulation. The paper give example of recordings from two different re-injection wells. The recordings from one of the re-injection wells show that there are serious problems in the well, while the other one shows "normal" hydraulic behavior

The use of a geological model in a cavern construction in limestone

Active design is an expression that has been used fore some years now. This paper will present a case study from an excavation of two cavern constructions (80m long x 16m wide x 12m high) and access tunnels in a Bryozoan limestone in southern Sweden. By using various geophysical survey methods like for instance resistivity soundings, in combination with core drilling and geophysical well logs a geological model of the proposed construction site could be created. In this process not only the geological composition was studied but also the physical properties of the limestone was investigated. The geological model gave indication of how the final design of the caverns should be carried out to overcome problems with fault zones and ground water intrusion. During the excavation of the limestone from the cavern rooms, geological surveys were carried out to assist in the event of a redesign of the cavern constructions. The active calibration of the geological model made it possible to change and reduce the reinforcement of the rock mass. Measurements of the overburden were also taken during the excavation to monitor the setting/compaction of the limestone cover. After the cavern constructions were completed but before the final lining of the rooms, the limestone exposed at cavern walls and roof were surveyed i.e. the induration and fracturing was determined. This was done in an attempt to calibrate and validate the geological model. By active design and calibration of the geological model during the complete excavation, it has been possible to optimize both the location as well as the final cavern design. For the purpose of this article it has also been possible to reveal the actual geological explanations supporting the basic geological model