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Selected AbstractsExamining the relationships between the Pro12Ala variant in PPARG and Type 2 diabetes-related traits in UK samplesDIABETIC MEDICINE, Issue 12 2005E. Zeggini Abstract Aims The Pro12Ala polymorphism in the PPARG gene alters amino acid sequence and has shown consistent association with susceptibility to Type 2 diabetes in several populations. The present study makes use of large, well-characterized case-control resources to enhance understanding of this susceptibility effect by examining related traits, such as body mass index (BMI), waist,hip ratio and age at diagnosis. Methods The Pro12Ala variant was genotyped in two UK case samples, ascertained for positive family history and/or early onset of Type 2 diabetes (combined n = 971); and in 1257 ethnically matched control subjects. Results There were significant associations of the Pro12Ala single nucleotide polymorphism (SNP) genotypes with diabetes in both case-control comparisons (P = 0.025 and P = 0.039). Comparing individuals homozygous for the Pro allele, with those carrying an Ala allele, the combined odds ratio for diabetes was 1.40 (95% CIs, 1.12,1.76, P = 0.0031). There was no association between the variant and either waist,hip ratio or age at diagnosis. Proline homozygosity was associated with increased BMI in one patient group (P = 0.013) and decreased BMI in the other (P = 0.038). Conclusions This study confirms that variation within PPARG influences susceptibility to Type 2 diabetes in UK samples. However, the relationship between PPARG variation and BMI is more complex, and studies in much larger sample sets will be required to more precisely characterize the effect of this variant on adiposity. [source] Meta-analysis: mortality in Crohn's diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2007C. CANAVAN SUMMARY Aim To perform a meta-analysis is of published literature reporting standardized mortality ratios (SMR) for Crohn's patients from 1970 to date. Methods Medline search identified relevant papers. Exploding references identified additional papers. When two papers reviewed mortality of one patient group at different times, the later publication was used. Results Of 13 papers identified, three studies reported SMR below 1.0, two others had confidence intervals including 1.0. All other studies reported mortality higher than the general population. Meta-analysis using a random effects model shows the pooled estimate for SMR in Crohn's disease is 1.52 (95% CI: 1.32 to 1.74 [P < 0.0001]). Meta-regression shows the SMR for these patients has decreased slightly over the past 30 years, but this decrease is not statistically significant (P = 0.08). Conclusion Assessing evidence from original studies and conducting a meta-analysis shows age-adjusted mortality risk from Crohn's disease is over 50% greater than the general population. Whilst mortality has improved since the condition was first recognized, further evaluation of the patients studied in the cohorts included here is necessary to assess more recent changes in clinical practice. [source] Reported food allergy to peanut, tree nuts and fruit: comparison of clinical manifestations, prescription of medication and impact on daily lifeALLERGY, Issue 7 2008T. M. Le Background: Peanut (PN), tree nuts (TN) and fruits are frequent causes of food allergy (FA). Peanut and TN are believed to cause more severe reactions than fruits. However, there are no studies comparing the severity of PN, TN and fruit allergy within one patient group. Methods: Four-hundred and eleven adult patients referred to our tertiary allergy center with suspicion of FA completed a standardized questionnaire. Patients with a typical history of immunoglubulin E (IgE)-mediated allergy, e.g. oropharyngeal symptoms to PN, TN (hazelnut, walnut, cashew nut) or fruit (apple, kiwi, peach, pear and cherry) were recruited (218/411). The objective was to evaluate differences in clinical severity between PN, TN and fruit allergy and how this was reflected by prescription of emergency medication and impact on daily life. Results: Eighty-two percent of the included 218 patients were sensitized to the respective foods. The percentages of severe symptoms (i.e. respiratory or cardiovascular symptoms) in PN, TN and fruit allergic patients were respectively 47%, 39% and 31% (respiratory) and 11%, 5.0% and 3.4% (cardiovascular). Prescription and use of emergency medication (epinephrine, antihistamines and steroids) did not differ among the three groups. The majority of patients with a PN or TN allergy (72%) and fruit allergy (62%) reported that FA influences their daily life considerably. Conclusions: Fruit allergy causes less severe symptoms than TN and especially PN allergy. However, this is not reflected in the prescription or use of emergency medication. This may indicate that physicians are not fully acquainted with the guidelines for prescription of emergency medication. A high impact on daily life was found both in PN, TN and in fruit allergy. [source] Kiwifruit allergy: actinidin is not a major allergen in the United KingdomCLINICAL & EXPERIMENTAL ALLERGY, Issue 9 2007J. S. A. Lucas Summary Background Actinidin has previously been reported as the major allergen in kiwifruit. Objectives To investigate the relevance of actinidin in a well-characterized population of UK patients with kiwifruit allergy. Methods To identify the allergens in kiwifruit, using Western blots, we examined the IgE-binding patterns of 76 patients with a history of kiwifruit allergy, 23 of who had had a positive double-blind, placebo-controlled food challenge. In addition, IgE binding to purified native actinidin was studied in 30 patients, and to acidic and basic isoforms of recombinant actinidin in five patients. Inhibition of IgE binding to kiwifruit protein extract by purified native actinidin was investigated by both inhibition immunoblots and inhibition ELISAs using pooled sera. Results Twelve protein bands in kiwifruit protein extract were bound by IgE. A protein band with a molecular weight of 38 kDa was the major allergen recognized by 59% of the population. IgE did not bind to actinidin in the kiwifruit protein extract, or to purified native or recombinant forms of actinidin during Western blotting. Pooled sera bound to kiwifruit protein extract but not purified actinidin on ELISA, and pre-incubating sera with actinidin did not inhibit IgE binding to kiwifruit protein extract on immunoblot or ELISA. Conclusion A novel 38 kDa protein, not actinidin, is the major allergen in this large study population. Identification of major allergens in one patient group is therefore not necessarily reproducible in another; therefore, major allergens should not be defined until there is a sufficient body of data from diverse geographical and cultural populations. [source] |