Epidemiological studies suggest that allergy risk is preferentially transmitted through mothers. This can be due to genomic imprinting, where the phenotype effect of an allele depends on its parental ...origin, or due to maternal effects reflecting the maternal genome's influence on the child during prenatal development. Loss-of-function mutations in the filaggrin gene (FLG) cause skin barrier deficiency and strongly predispose to atopic dermatitis (AD). We investigated the 4 most prevalent European FLG mutations (c.2282del4, p.R501X, p.R2447X, and p.S3247X) in two samples including 759 and 450 AD families. We used the multinomial and maximum-likelihood approach implemented in the PREMIM/EMIM tool to model parent-of-origin effects. Beyond the known role of FLG inheritance in AD (R1meta-analysis = 2.4, P = 1.0 x 10-36), we observed a strong maternal FLG genotype effect that was consistent in both independent family sets and for all 4 mutations analysed. Overall, children of FLG-carrier mothers had a 1.5-fold increased AD risk (S1 = 1.50, Pmeta-analysis = 8.4 x 10-8). Our data point to two independent and additive effects of FLG mutations: i) carrying a mutation and ii) having a mutation carrier mother. The maternal genotype effect was independent of mutation inheritance and can be seen as a non-genetic transmission of a genetic effect. The FLG maternal effect was observed only when mothers had allergic sensitization (elevated allergen-specific IgE antibody plasma levels), suggesting that FLG mutation-induced systemic immune responses in the mother may influence AD risk in the child. Notably, the maternal effect reported here was stronger than most common genetic risk factors for AD recently identified through genome-wide association studies (GWAS). Our study highlights the power of family-based studies in the identification of new etiological mechanisms and reveals, for the first time, a direct influence of the maternal genotype on the offspring's susceptibility to a common human disease.
Atopic dermatitis is a common inflammatory skin disease with a strong heritable component. Pathogenetic models consider keratinocyte differentiation defects and immune alterations as scaffolds, and ...recent data indicate a role for autoreactivity in at least a subgroup of patients. FLG (encoding filaggrin) has been identified as a major locus causing skin barrier deficiency. To better define risk variants and identify additional susceptibility loci, we densely genotyped 2,425 German individuals with atopic dermatitis (cases) and 5,449 controls using the Immunochip array followed by replication in 7,196 cases and 15,480 controls from Germany, Ireland, Japan and China. We identified four new susceptibility loci for atopic dermatitis and replicated previous associations. This brings the number of atopic dermatitis risk loci reported in individuals of European ancestry to 11. We estimate that these susceptibility loci together account for 14.4% of the heritability for atopic dermatitis.
Background Atopic dermatitis (AD) is a common inflammatory skin disease. Previous studies have revealed shared genetic determinants among different inflammatory disorders, suggesting that markers ...associated with immune-related traits might also play a role in AD. Objective We sought to identify novel genetic risk factors for AD. Methods We examined the results of all genome-wide association studies from a public repository and selected 318 genetic markers that were significantly associated with any inflammatory trait. These markers were considered candidates and tested for association with AD in a 3-step approach including 7 study populations with 7130 patients with AD and 9253 control subjects. Results A functional amino acid change in the IL-6 receptor (IL-6R Asp358Ala; rs2228145) was significantly associated with AD (odds ratio OR, 1.15; P = 5 × 10−9 ). Interestingly, investigation of 2 independent population-based birth cohorts showed that IL-6R 358Ala specifically predisposes to the persistent form of AD (ORpersistent AD = 1.22, P = .0008; ORtransient AD = 1.04, P = .54). This variant determines the balance between the classical membrane-bound versus soluble IL-6R signaling pathways. Carriers of 358Ala had increased serum levels of soluble IL-6R ( P = 4 × 10−14 ), with homozygote carriers showing a 2-fold increase. Moreover, we demonstrate that soluble IL-6R levels were higher in patients with AD than in control subjects (46.0 vs 37.8 ng/mL, P = .001). Additional AD risk variants were identified in RAD50 , RUNX3 , and ERBB3. Conclusion Our study supports the importance of genetic variants influencing inflammation in the etiology of AD. Moreover, we identified a functional genetic variant in IL6R influencing disease prognosis and specifically predisposing to persistent AD.
This study examined two potential mediators through which leaders transmit their position power into an effectiveness outcome. Drawing upon recent work integrating trait, situational, and behavioral ...theories of leadership effectiveness, we hypothesized and tested a model specifying that the interactive effects of leader position power and leader political skill on follower satisfaction would be mediated by followers’ perceptions of leaders’ initiating structure and consideration behaviors. Specifically, this model indicates that leaders who are both in powerful positions and politically skilled are perceived to initiate more structure and demonstrate more consideration for their followers than their nonpolitically skilled counterparts, which, in turn, positively impacts followers’ satisfaction (i.e., an indication of subjective leadership effectiveness). Utilizing 190 leaders and 476 followers, we found support for the hypothesized model. Contributions to various literatures, strengths, limitations, and practical implications are discussed.
Epidemiological studies suggest that allergy risk is preferentially transmitted through mothers. This can be due to genomic imprinting, where the phenotype effect of an allele depends on its parental ...origin, or due to maternal effects reflecting the maternal genome's influence on the child during prenatal development. Loss-of-function mutations in the filaggrin gene (FLG) cause skin barrier deficiency and strongly predispose to atopic dermatitis (AD). We investigated the 4 most prevalent European FLG mutations (c.2282del4, p.R501X, p.R2447X, and p.S3247X) in two samples including 759 and 450 AD families. We used the multinomial and maximum-likelihood approach implemented in the PREMIM/EMIM tool to model parent-of-origin effects. Beyond the known role of FLG inheritance in AD (R1meta-analysis = 2.4, P = 1.0 x 10-36), we observed a strong maternal FLG genotype effect that was consistent in both independent family sets and for all 4 mutations analysed. Overall, children of FLG-carrier mothers had a 1.5-fold increased AD risk (S1 = 1.50, Pmeta-analysis = 8.4 x 10-8). Our data point to two independent and additive effects of FLG mutations: i) carrying a mutation and ii) having a mutation carrier mother. The maternal genotype effect was independent of mutation inheritance and can be seen as a non-genetic transmission of a genetic effect. The FLG maternal effect was observed only when mothers had allergic sensitization (elevated allergen-specific IgE antibody plasma levels), suggesting that FLG mutation-induced systemic immune responses in the mother may influence AD risk in the child. Notably, the maternal effect reported here was stronger than most common genetic risk factors for AD recently identified through genome-wide association studies (GWAS). Our study highlights the power of family-based studies in the identification of new etiological mechanisms and reveals, for the first time, a direct influence of the maternal genotype on the offspring's susceptibility to a common human disease.
The antimicrobial susceptibility of coagulase-negative staphylococci isolated from spontaneously fermented sausages was assessed using both traditional and molecular methods. Isolates were tested for ...sensitivity to vancomycin, ampicillin, erythromycin, tetracycline, gentamycin and oxacillin by the disk diffusion method and quantitative-qualitative epsilometer test. PCR was used for the detection of resistance genes mecA, ermB, tetK and tetM. The identified coagulase-negative staphylococci were Staphylococcus epidermidis (69 %), S. capitis (5 %) and S. warneri (2.5 %). S. epidermidis showed a high rate of phenotypical resistance to tetracycline and erythromycin (44.4 % of strains). Molecular evaluation of resistance determinants revealed tetK or tetM genes in eight S. epidermidis strains. Although S. epidermidis is not classical food poisoning bacteria, its presence in food could be of public health significance due to the possible spread of antimicrobial resistance determinants. Our findings implicate that spontaneous meat fermentation could result in products with a potential hazard to consumers.
U radu je primjenom klasičnih i molekularnih metoda istražena osjetljivost koagulaza-negativnih stafilokoka iz tradicionalnih fermentiranih kobasica na antimikrobne spojeve. Pomoću disk-difuzijskog i ...epsilometar testa ispitana je osjetljivost izolata na vankomicin, ampicilin, eritromicin, tetraciklin, gentamicin i oksacilin. Metodom je PCR u izolatima određena prisutnost gena za rezistenciju, i to mecA, ermB, tetK i tetM. Utvrđene su sljedeće vrste koagulaza-negativnih stafilokoka: Staphylococcus epidermidis (69 %), S. capitis (5 %) i S. warneri (2.5 %). Ukupno je 44,4 % izolata S. epidermidis pokazalo fenotipsku rezistenciju na tetraciklin i eritromicin. Prisutnost gena tetK ili tetM potvrđena je u 8 izolata S. epidermidis. Iako S. epidermidis nije uobičajeni uzročnik trovanja hranom, njegova je prisutnost u hrani važna za javno zdravstvo zbog mogućeg širenja antimikrobne rezistencije. Dobiveni rezultati pokazuju da spontanom fermentacijom mesa mogu nastati proizvodi opasni za zdravlje potrošača.
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