Exploring the role and transformative potential of human rights in development practice and food security : case study from Malawi

Avhandlingen är en analys av den roll som mänskliga rättigheter spelar i utvecklingssamarbete i allmänhet och tre matsäkerhetsprojekt i Malawi i synnerhet. Författaren undersöker huruvida mänskliga rättigheter kan bidra till samhälleliga förändringsprocesser. Undersökningen har en diskursiv syn på mänskliga rättigheter; rättigheter ses som sociala konstruktioner skapade av människor, konstruktioner som förändras i takt med att aktörerna ger dem ny mening. Människorättsbaserade utvecklingsstrategier riktar uppmärksamheten mot olika aktörers skyldigheter samt vikten av att mänskliga rättigheter inte kränks genom utvecklingspolitiska beslut. En analys som utgår från mänskliga rättigheter kan leda till att nya frågor lyfts fram: vem har skyldigheter, vem har rättigheter, och varför förverkligas inte dessa? Fokus flyttas till hur politiska, ekonomiska och juridiska strukturer kan förändras så att de främjar mänskliga rättigheter. Författaren använder empiriskt material från Malawi för att visa vilken roll mänskliga rättigheter och så kallade människorättsprinciper spelar inom tre projekt: (1) ett mathjälpsprojekt; (2) ett rättighetsbaserat projekt med fokus på att stärka strategier för livsuppehälle; (3) ett juridiskt projekt inom ramen för vilket man skapat ett lagförslag om rätten till föda. Analysen visar att det rättighetsbaserade projektet strävade efter den mest djupgående samhälleliga förändringen. Människorättsprinciperna ansvarighet och deltagande handlade inte endast om verksamheten inom projektet utan man strävade även efter att stärka dessa principer mellan medborgare och myndigheter. Rättigheter, som ett sätt att tala, tänka och handla, inte som abstrakta juridiska normer, påverkade de lokala aktörernas sätt att kräva bl.a. tjänster av lokala myndigheter. Teoretiskt kan man säga att det rättighetsbaserade projektet representerar ett aktörsperspektiv på mänskliga rättigheter där aktörernas egna uppfattningar om vad de är berättigade till samt krav på myndigheters ansvar formade vilken mening rättigheterna kom att få.

Role of the canonical transient receptor potential channel 2 (TRPC2) in thyroid cell function

Kalciumjonen reglerar flera processer i celler såsom transkribering av gener, celldelning, cellernas rörlighet och celldöd. Därför har cellerna utvecklat många mekanismer för att reglera den intracellulära kalciumkoncentrationen. Kalciumkanaler spelar en viktig roll i denna regleringsprocess. TRPC-kanalerna (eng. canonical transient receptor potential) är en familj av jonkanaler med sju medlemmar (TRPC1-7) vars regleringsmekanismer och fysiologiska roller är varierande. TRPC2-kanalens fysiologiska signifikans, samt hur kanalen regleras, är dåligt karakteriserad. För första gången, rapporterar vi närvaron av TRPC2 kanalen i råttans sköldkörtelceller samt primära sköldkörtelceller från råtta. Hos gnagare har TRPC2 antagits vara exklusivt uttryckt i det vomeronasala organet. För att undersöka den fysiologiska betydelsen av kanalen, har vi utvecklat stabila celler med nedreglerat TRPC2 (shTRPC2) m.h.a. shRNA-teknik. Nedreglering av TRPC2 resulterade i stora skillnader i flera viktiga cellulära funktioner och i regleringen av sköldkörtelcellernas cellsignalering. Nedreglering av TRPC2 orsakade minskad agonist-beroende frigivning av kalcium från det endoplasmatiska nätverket, samt minskat agonist-beroende inflöde av extracellulärt kalcium, men ökade det basala kalciuminflödet. Uttrycket av PKCβ1 och PKCδ, SERCA-aktiviteten och kalciumhalten i det endoplasmatiska nätverket minskade i shTRPC2 celler. Kommunikation mellan kalcium- och cAMP-signalering påvisades vara TRPC2-beroende, vilket visades reglera uttrycket av TSH-receptorn. Vi undersökte också betydelsen av TRPC2 kanalen i reglering av sköldkörtelcellers proliferation, migration, vidhäftning och invasion; processer som alla var dämpade i shTRPC2 celler. Samamnfattningsvis påvisade dessa resultat en ny och viktig fysiologisk betydelse för TRPC2 kanalerna.

Potential pathogenic role of aggregative- adhering Corynebacterium diphtheriae of different clonal groups in endocarditis

Invasive diseases caused by Corynebacterium diphtheriae have been described increasingly. Several reports indicate the destructive feature of endocarditis attributable to nontoxigenic strains. However, few reports have dealt with the pathogenicity of invasive strains. The present investigation demonstrates a phenotypic trait that may be used to identify potentially invasive strains. The study also draws attention to clinical and microbiological aspects observed in 5 cases of endocarditis due to C. diphtheriae that occurred outside Europe. Four cases occurred in female school-age children (7-14 years) treated at different hospitals in Rio de Janeiro, Brazil. All patients developed other complications including septicemia, renal failure and/or arthritis. Surgical treatment was performed on 2 patients for valve replacement. Lethality was observed in 40% of the cases. Microorganisms isolated from 5 blood samples and identified as C. diphtheriae subsp mitis (N = 4) and C. diphtheriae subsp gravis (N = 1) displayed an aggregative adherence pattern to HEp-2 cells and identical one-dimensional SDS-PAGE protein profiles. Aggregative-adhering invasive strains of C. diphtheriae showed 5 distinct RAPD profiles. Despite the clonal diversity, all 5 C. diphtheriae invasive isolates seemed to display special bacterial adhesive properties that may favor blood-barrier disruption and systemic dissemination of bacteria. In conclusion, blood isolates from patients with endocarditis exhibited a unique adhering pattern, suggesting a pathogenic role of aggregative-adhering C. diphtheriae of different clones in endocarditis. Accordingly, the aggregative-adherence pattern may be used as an indication of some invasive potential of C. diphtheriae strains.

Investigating the role of potential genetic markers that can predict risk for steroid refractory inflammatory bowel disease

Contexte - La variation interindividuelle de la réponse aux corticostéroïdes (CS) est un problème important chez les patients atteints de maladies inflammatoires d’intestin. Ce problème est bien plus accentué chez les enfants avec la prévalence de la corticodépendance extrêmement (~40 %) élevée. La maladie réfractaire au CS a des répercussions sur le développement et le bien-être physique et psychologique des patients et impose des coûts médicaux élevés, particulièrement avec la maladie active comparativement à la maladie en rémission, le coût étant 2-3 fois plus élevé en ambulatoire et 20 fois plus élevé en hôpital. Il est ainsi primordial de déterminer les marqueurs prédictifs de la réponse aux CS. Les efforts précédents de découvrir les marqueurs cliniques et démographiques ont été équivoques, ce qui souligne davantage le besoin de marqueurs moléculaires. L'action des CS se base sur des processus complexes déterminés génétiquement. Deux gènes, le ABCB1, appartenant à la famille des transporteurs transmembraneaux, et le NR3C1, encodant le récepteur glucocorticoïde, sont des éléments importants des voies métaboliques. Nous avons postulé que les variations dans ces gènes ont un rôle dans la variabilité observée de la réponse aux CS et pourraient servir en tant que les marqueurs prédictifs. Objectifs - Nous avons visé à: (1) examiner le fardeau de la maladie réfractaire aux CS chez les enfants avec la maladie de Crohn (MC) et le rôle des caractéristiques cliniques et démographiques potentiellement liés à la réponse; (2) étudier l'association entre les variantes d'ADN de gène ABCB1 et la réponse aux CS; (3) étudier les associations entre les variantes d'ADN de gène NR3C1 et la réponse aux CS. Méthodes - Afin d’atteindre ces objectifs, nous avons mené une étude de cohorte des patients recrutés dans deux cliniques pédiatriques tertiaires de gastroentérologie à l’Ottawa (CHEO) et à Montréal (HSJ). Les patients avec la MC ont été diagnostiqués avant l'âge de 18 ans selon les critères standard radiologiques, endoscopiques et histopathologiques. La corticorésistance et la corticodépendance ont été définies en adaptant les critères reconnus. L’ADN, acquise soit du sang ou de la salive, était génotypée pour des variations à travers de gènes ABCB1 et NR3C1 sélectionnées à l’aide de la méthodologie de tag-SNP. La fréquence de la corticorésistance et la corticodépendance a été estimée assumant une distribution binomiale. Les associations entre les variables cliniques/démographiques et la réponse aux CS ont été examinées en utilisant la régression logistique en ajustant pour des variables potentielles de confusion. Les associations entre variantes génétiques de ABCB1 et NR3C1 et la réponse aux CS ont été examinées en utilisant la régression logistique assumant différents modèles de la transmission. Les associations multimarqueurs ont été examinées en utilisant l'analyse de haplotypes. Les variantes nongénotypées ont été imputées en utilisant les données de HAPMAP et les associations avec SNPs imputés ont été examinées en utilisant des méthodes standard. Résultats - Parmi 645 patients avec la MC, 364 (56.2%) ont reçu CS. La majorité de patients étaient des hommes (54.9 %); présentaient la maladie de l’iléocôlon (51.7%) ou la maladie inflammatoire (84.6%) au diagnostic et étaient les Caucasiens (95.6 %). Huit pourcents de patients étaient corticorésistants et 40.9% - corticodépendants. Le plus bas âge au diagnostic (OR=1.34, 95% CI: 1.03-3.01, p=0.040), la maladie cœxistante de la région digestive supérieure (OR=1.35, 95% CI: 95% CI: 1.06-3.07, p=0.031) et l’usage simultané des immunomodulateurs (OR=0.35, 95% CI: 0.16-0.75, p=0.007) ont été associés avec la corticodépendance. Un total de 27 marqueurs génotypés à travers de ABCB1 (n=14) et NR3C1 (n=13) ont été en l'Équilibre de Hardy-Weinberg, à l’exception d’un dans le gène NR3C1 (rs258751, exclu). Dans ABCB1, l'allèle rare de rs2032583 (OR=0.56, 95% CI: 0.34-0.95, p=0.029) et génotype hétérozygote (OR=0.52, 95% CI: 0.28-0.95 p=0.035) ont été négativement associes avec la dépendance de CS. Un haplotype à 3 marqueurs, comprenant le SNP fonctionnel rs1045642 a été associé avec la dépendance de CS (p empirique=0.004). 24 SNPs imputés introniques et six haplotypes ont été significativement associés avec la dépendance de CS. Aucune de ces associations n'a cependant maintenu la signification après des corrections pour des comparaisons multiples. Dans NR3C1, trois SNPs: rs10482682 (OR=1.43, 95% CI: 0.99-2.08, p=0.047), rs6196 (OR=0.55, 95% CI: 0.31-0.95, p=0.024), et rs2963155 (OR=0.64, 95% CI: 0.42-0.98, p=0.039), ont été associés sous un modèle additif, tandis que rs4912911 (OR=0.37, 95% CI: 0.13-1.00, p=0.03) et rs2963156 (OR=0.32, 95% CI: 0.07-1.12, p=0.047) - sous un modèle récessif. Deux haplotypes incluant ces 5 SNPs (AAACA et GGGCG) ont été significativement (p=0.006 et 0.01 empiriques) associés avec la corticodépendance. 19 SNPs imputés ont été associés avec la dépendance de CS. Deux haplotypes multimarqueurs (p=0.001), incluant les SNPs génotypés et imputés, ont été associés avec la dépendance de CS. Conclusion - Nos études suggèrent que le fardeau de la corticodépendance est élevé parmi les enfants avec le CD. Les enfants plus jeunes au diagnostic et ceux avec la maladie coexistante de la région supérieure ainsi que ceux avec des variations dans les gènes ABCB1 et NR3C1 étaient plus susceptibles de devenir corticodépendants.

The role of ligneous vegetation for livestock nutrition in the sub-Sahelian and Sudanian zones of West Africa: Potential effects of climate change

Climate change and variability in sub-Saharan West Africa is expected to have negative consequences for crop and livestock farming due to the strong dependence of these sectors on rainfall and natural resources, and the low adaptive capacity of crops farmers, agro-pastoralist and pastoralists in the region. The objective of this PhD research was to investigate the anticipated impacts of expected future climate change and variability on nutrition and grazing management of livestock in the prevailing extensive agro-pastoral and pastoral systems of the Sahelian and Sudanian zones of Burkina Faso. To achieve this, three studies were undertaken in selected village territories (100 km² each) in the southern Sahelian (Taffogo), northern Sudanian (Nobere, Safane) and southern Sudanian (Sokouraba) zone of the country during 2009 and 2010. The choice of two villages in the northern Sudanian zone was guided by the dichotomy between intense agricultural land use and high population density near Safane, and lower agricultural land use in the tampon zone between the village of Nobere and the National Park Kaboré Tambi of Pô. Using global positioning and geographical information systems tools, the spatio-temporal variation in the use of grazing areas by cattle, sheep and goats, and in their foraging behaviour in the four villages was assessed by monitoring three herds each per species during a one-year cycle (Chapter 2). Maximum itinerary lengths (km/d) were observed in the hot dry season (March-May); they were longer for sheep (18.8) and cattle (17.4) than for goats (10.5, p<0.05). Daily total grazing time spent on pasture ranged from 6 - 11 h with cattle staying longer on pasture than small ruminants (p<0.05). Feeding time accounted for 52% - 72% of daily time on pasture, irrespective of species. Herds spent longer time on pasture and walked farther distances in the southern Sahelian than the two Sudanian zones (p<0.01), while daily feeding time was longer in the southern Sudanian than in the other two zones (p>0.05). Proportional time spent resting decreased from the rainy (June - October) to the cool (November - February) and hot dry season (p<0.05), while in parallel the proportion of walking time increased. Feeding time of all species was to a significantly high proportion spent on wooded land (tree crown cover 5-10%, or shrub cover >10%) in the southern Sahelian zone, and on forest land (tree crown cover >10%) in the two Sudanian zones, irrespective of season. It is concluded that with the expansion of cropland in the whole region, remaining islands of wooded land, including also fields fallowed for three or more years with their considerable shrub cover, are particularly valuable pasturing areas for ruminant stock. Measures must be taken that counteract the shrinking of wooded land and forests across the whole region, including also active protection and (re)establishment of drought-tolerant fodder trees. Observation of the selection behaviour of the above herds of cattle and small ruminant as far as browse species were concerned, and interviews with 75 of Fulani livestock keepers on use of browse as feed by their ruminant stock and as remedies for animal disease treatment was undertaken (Chapter 3) in order to evaluate the consequence of climate change for the contribution of browse to livestock nutrition and animal health in the extensive grazing-based livestock systems. The results indicated that grazing cattle and small ruminants do make considerable use of browse species on pasture across the studied agro-ecological zones. Goats spent more time (p<0.01) feeding on browse species than sheep and cattle, which spent a low to moderate proportion of their feeding time on browsing in any of the study sites. As far as the agro-ecological zones were concerned, the contribution of browse species to livestock nutrition was more important in the southern Sahelian and northern Sudanian zone than the southern Sudanian zone, and this contribution is higher during the cold and hot dry season than during the rainy season. A total of 75 browse species were selected on pasture year around, whereby cattle strongly preferred Afzelia africana, Pterocarpus erinaceus and Piliostigma sp., while sheep and goats primarily fed on Balanites aegyptiaca, Ziziphus mauritiana and Acacia sp. Crude protein concentration (in DM) of pods or fruits of the most important browse species selected by goats, sheep and cattle ranged from 7% to 13% for pods, and from 10% to 18% for foliage. The concentration of digestible organic matter of preferred browse species mostly ranged from 40% to 60%, and the concentrations of total phenols, condensed tannins and acid detergent lignin were low. Linear regression analyses showed that browse preference on pasture is strongly related to its contents (% of DM) of CP, ADF, NDF and OM digestibility. Interviewed livestock keepers reported that browse species are increasingly use by their grazing animals, while for animal health care use of tree- and shrub-based remedies decreased over the last two decades. It is concluded that due to climate change with expected negative impact on the productivity of the herbaceous layer of communal pastures browse fodder will gain in importance for animal nutrition. Therefore re-establishment and dissemination of locally adapted browse species preferred by ruminants is needed to increase the nutritional situation of ruminant stock in the region and contribute to species diversity and soil fertility restoration in degraded pasture areas. In Chapter 4 a combination of household surveys and participatory research approaches was used in the four villages, and additionally in the village of Zogoré (southern Sahelian zone) and of Karangasso Vigué (northern Sudanian zone) to investigate pastoralists’ (n= 76) and agro-pastoralists’ (n= 83) perception of climate change, and their adaptation strategies in crop and livestock production at farm level. Across the three agro-ecological zones, the majority of the interviewees perceived an increase in maximum day temperatures and decrease of total annual rainfall over the last two decades. Perceptions of change in climate patterns were in line with meteorological data for increased temperatures while for total rainfall farmers’ views contrasted the rainfall records which showed a slight increase of precipitation. According to all interviewees climate change and variability have negative impacts on their crop and animal husbandry, and most of them already adopted some coping and adaptation strategies at farm level to secure their livelihoods and reduce negative impacts on their farming system. Although these strategies are valuable and can help crop and livestock farmers to cope with the recurrent droughts and climate variability, they are not effective against expected extreme climate events. Governmental and non-governmental organisations should develop effective policies and strategies at local, regional and national level to support farmers in their endeavours to cope with climate change phenomena; measures should be site-specific and take into account farmers’ experiences and strategies already in place.

Increasing scepticism toward potential liars: effects of existential threat on veracity judgments and the moderating role of honesty norm activation

With the present research, we investigated effects of existential threat on veracity judgments. According to several meta-analyses, people judge potentially deceptive messages of other people as true rather than as false (so-called truth bias). This judgmental bias has been shown to depend on how people weigh the error of judging a true message as a lie (error 1) and the error of judging a lie as a true message (error 2). The weight of these errors has been further shown to be affected by situational variables. Given that research on terror management theory has found evidence that mortality salience (MS) increases the sensitivity toward the compliance of cultural norms, especially when they are of focal attention, we assumed that when the honesty norm is activated, MS affects judgmental error weighing and, consequently, judgmental biases. Specifically, activating the norm of honesty should decrease the weight of error 1 (the error of judging a true message as a lie) and increase the weight of error 2 (the error of judging a lie as a true message) when mortality is salient. In a first study, we found initial evidence for this assumption. Furthermore, the change in error weighing should reduce the truth bias, automatically resulting in better detection accuracy of actual lies and worse accuracy of actual true statements. In two further studies, we manipulated MS and honesty norm activation before participants judged several videos containing actual truths or lies. Results revealed evidence for our prediction. Moreover, in Study 3, the truth bias was increased after MS when group solidarity was previously emphasized.

Role and potential influence of technologies on the most relevant challenges for long-term care. ENEPRI Research Report No. 113, 26 June 2012

This report considers three case studies (namely diabetes, dementia and obesity) for setting up a framework to assess the systemic influences of technologies in the long-term care milieu, using a problem-driven approach in relation to health care. Such technologies could be an enabling factor or a catalyser of advances taking place in the health and social sectors. They offer opportunities to support and amplify relevant organisational changes in the context of innovative care models, which stem from overall policies and regulations of a national or regional jurisdiction to address the future sustainability of health and social care.

Song development in birds: the role of early experience and its potential effect on rehabilitation success

Environmental conditions during the early life stages of birds can have significant effects on the quality of sexual signals in adulthood, especially song, and these ultimately have consequences for breeding success and fitness. This has wide-ranging implications for the rehabilitation protocols undertaken in wildlife hospitals which aim to return captive-reared animals to their natural habitat. Here we review the current literature on bird song development and learning in order to determine the potential impact that the rearing of juvenile songbirds in captivity can have on rehabilitation success. We quantify the effects of reduced learning on song structure and relate this to the possible effects on an individual's ability to defend a territory or attract a mate. We show the importance of providing a conspecific auditory model for birds to learn from in the early stages post-fledging, either via live- or tape-tutoring and provide suggestions for tutoring regimes. We also highlight the historical focus on learning in a few model species that has left an information gap in our knowledge for most species reared at wildlife hospitals.

Heat-inactivated peroxidases and the role of calcium abstraction as a cause of their enhanced lipid oxidation activity: potential effects on the flavour quality of heat-processed vegetables

Cationic swede and anionic turnip peroxidases were partially purified by ion-exchange and gel-filtration chromatography, respectively. Heat treatment of these enzymes and of a commercial high purity horseradish peroxidase (HRP) caused a loss of enzyme activity and a corresponding increase in linoleic acid hydroperoxide formation activity. The hydroperoxide levels in model systems increased only in the early stages of the oxidation reaction and then declined as degradation became more significant. The presence of a dialysed blend of cooked swede markedly lowered the hydroperoxide level formed. Analysis of volatile compounds formed showed that hexanal predominated in a buffer system and in a blend of cooked turnip. In dialysed blends of cooked swede, hexanol was the primary volatile compound generated. After inactivation under mild conditions in the presence of EDTA, the peroxidases showed hydroperoxide formation activity and patterns of volatile compounds from linoleic acid that were similar to those found on heat-inactivation. This suggested that calcium abstraction from the peroxidases was critical for the enhancement of lipid oxidation activity. (C) 2002 Elsevier Science Ltd. All rights reserved.

Role of transient receptor potential vanilloid 4 in rat joint inflammation

Objective To determine whether activation of transient receptor potential vanilloid 4 (TRPV-4) induces inflammation in the rat temporomandibular joint (TMJ), and to assess the effects of TRPV-4 agonists and proinflammatory mediators, such as a protease-activated receptor 2 (PAR-2) agonist, on TRPV-4 responses. Methods Four hours after intraarticular injection of carrageenan into the rat joints, expression of TRPV-4 and PAR-2 in trigeminal ganglion (TG) neurons and in the TMJs were evaluated by real-time reverse transcriptionpolymerase chain reaction and immunofluorescence, followed by confocal microscopy. The functionality of TRPV-4 and its sensitization by a PAR-2activating peptide (PAR-2AP) were analyzed by measuring the intracellular Ca2+ concentration in TMJ fibroblast-like synovial cells or TG neurons. Plasma extravasation, myeloperoxidase activity, and the head-withdrawal threshold (index of mechanical allodynia) were evaluated after intraarticular injection of selective TRPV-4 agonists, either injected alone or coinjected with PAR-2AP. Results In the rat TMJs, TRPV-4 and PAR-2 expression levels were up-regulated after the induction of inflammation. Two TRPV-4 agonists specifically activated calcium influx in TMJ fibroblast-like synovial cells or TG neurons. In vivo, the agonists triggered dose-dependent increases in plasma extravasation, myeloperoxidase activity, and mechanical allodynia. In synovial cells or TG neurons, pretreatment with PAR-2AP potentiated a TRPV-4 agonistinduced increase in [Ca2+]i. In addition, TRPV-4 agonistinduced inflammation was potentiated by PAR-2AP in vivo. Conclusion In this rat model, TRPV-4 is expressed and functional in TG neurons and synovial cells, and activation of TRPV-4 in vivo causes inflammation in the TMJ. Proinflammatory mediators, such as PAR-2 agonists, sensitize the activity of TRPV-4. These results identify TRPV-4 as an important signal of inflammation in the joint.

Rare-earth impurities in gallium nitride: The role of the Hubbard potential

We performed a first principles investigation on the electronic properties of 4f-rare earth substitutional impurities in zincblende gallium nitride (GaN:REGa, with RE=Eu, Gd, Tb, Dy, Ho, Er and Tm). The calculations were performed within the all electron methodology and the density functional theory. We investigated how the introduction of the on-site Hubbard U potential (GGA + U) corrects the electronic properties of those impurities. We showed that a self-consistent procedure to compute the Hubbard potential provides a reliable description on the position of the 4f-related energy levels with respect of the GaN valence band top. The results were compared to available data coming from a recent phenomenological model. (C) 2012 Elsevier B.V. All rights reserved.

Potential vorticity conserving flows and vortex-wave interaction : the role of vertical velocity and isopycnal diffusion on plankton heterogeneity

Programa de doctorado de oceanografía

A role for GRK2 in myocardial ischemic injury: indicators of a potential future therapy and diagnostic

Morbidity and mortality of myocardial infarction remains significant with resulting left ventricular function presenting as a major determinant of clinical outcome. Protecting the myocardium against ischemia reperfusion injury has become a major therapeutic goal and the identification of key signaling pathways has paved the way for various interventions, but until now with disappointing results. This article describes the recently discovered new role of G-protein-coupled receptor kinase-2 (GRK2), which is known to critically influence the development and progression of heart failure, in acute myocardial injury. This article focuses on potential applications of the GRK2 peptide inhibitor βARKct in ischemic myocardial injury, the use of GRK2 as a biomarker in acute myocardial infarction and discusses the challenges of translating GRK2 inhibition as a cardioprotective strategy to a possible future clinical application.

Role of the NFKB1 -94ins/delATTG promoter polymorphism in IBD and potential interactions with polymorphisms in the CARD15/NOD2, IKBL, and IL-1RN genes

BACKGROUND: Recently, an association of the NFKB1 polymorphism -94ins/delATTG with ulcerative colitis (UC) has been reported. This 4-bp insertion/deletion polymorphism is localized in the promoter region of the NFKB1 gene and appears to be functionally relevant. The aim of the present study was to confirm the association of the -94ins/delATTG (W/D) NFKB1 promoter polymorphism with UC in a population of German origin and to test for a potential association with Crohn's disease (CD). Furthermore, potential interactions of the -94ins/delATTG polymorphism with the IKBL and the IL-1RN genes should be determined. MATERIALS AND METHODS: The study population comprised 630 patients with CD, 365 patients with UC, and 974 healthy controls. Genotyping was performed using polymerase chain reaction and restriction fragment length polymorphism analysis. For statistical evaluation, the chi-square test and the Fisher exact test were used. RESULTS: No significant association of the W/D NFKB1 polymorphism with CD or UC was detected. In addition, no significant interactions between the -94ins/delATTG NFKB1 polymorphism and polymorphisms within the IKBL and the IL-1RN genes, respectively, were found in CD or UC. Also, no significant interactions of the NFKB1 polymorphism with mutations of the CARD15/NOD2 gene and with clinical phenotypes were detected in CD. Moreover, no associations of the NFKB1 polymorphism were found in UC depending on disease localization. CONCLUSIONS: The present study could not confirm the reported association of the -94ins/delATTG NFKB1 polymorphism with UC and also found no evidence for a role of this polymorphism in CD. The results do not give evidence for a role of this NFKB1 polymorphism in the pathogenesis of UC and CD.