An Overall Evaluation Of The Resistance (r) And Pathogenesis-related (pr) Super Families In Soybean, As Compared With Medicago And Arabidopsis

Plants have the ability to recognize and respond to a multitude of pathogens, resulting in a massive reprogramming of the plant to activate defense responses including Resistance (R) and Pathogenesis-Related (PR) genes. Abiotic stresses can also activate PR genes and enhance pathogen resistance, representing valuable genes for breeding purposes. The present work offers an overview of soybean Rand PR genes present in the GENOSOJA (Brazilian Soybean Genome Consortium) platform, regarding their structure, abundance, evolution and role in the plant-pathogen metabolic pathway, as compared with Medicago and Arabidopsis. Searches revealed 3,065 R candidates (756 in Soybean, 1,142 in Medicago and 1,167 in Arabidopsis), and PR candidates matching to 1,261 sequences (310, 585 and 366 for the three species, respectively). The identified transcripts were also evaluated regarding their expression pattern in 65 libraries, showing prevalence in seeds and developing tissues. Upon consulting the Super SAGE libraries, 1,072 Rand 481 PR tags were identified in association with the different libraries. Multiple alignments were generated forXa21andPR-2genes, allowing inferences about their evolution. The results revealed interesting insights regarding the variability and complexity of defense genes in soybean, as compared with Medicago and Arabidopsis. © 2012, Sociedade Brasileira de Genética.35SUPPL.1260271Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., Walter, P., (2002) Molecular Biology of the Cell, p. 1616. , 4th edition. Garland Publishing Company, New York & LondonAltschul, S.F., Gish, W., Miller, W., Myers, E., Basic local alignment search tool (1990) J Mol Biol, 215, pp. 403-410Ashfield, T., Bocian, A., Held, D., Henk, A.D., Marek, L.F., Danesh, D., Penuela, S., Young, N.D., Genetic and physical localization of the soybean Rpg1-b disease resistance gene reveals a complex locus containing several tightly linked families of NBS-LRR genes (2003) Mol Plant Microbe Interact, 16, pp. 817-826Atici, O., Nalbantoglu, B., Antifreeze proteins in higher plants (2003) Phytochemistry, 64, pp. 1187-1196Barbosa-da-Silva, A., Wanderley-Nogueira, A.C., Silva, R.R.M., Belarmino, L.C., Soares-Cavalcanti, N.M., Benko-Iseppon, A.M., In silico survey of resistance (R) genes in Eucalyptus transcriptome (2005) Genet Mol Biol, 28, pp. 562-574Benko-Iseppon, A.M., Galdino, S.L., Calsa, T., Kido, E.A., Tossi, A., Belarmino, L.C., Crovella, S., Overview of plant antimicrobial peptides (2010) Curr Prot Pept Sci, 11, pp. 181-188Bent, A.F., Plant disease resistance genes: Function meets structure (1996) Plant Cell, 8, pp. 1751-1771Bolton, M., Primary metabolism and plant defense-Fuel for the fire (2009) Mol Plant Microbe Interact, 22, pp. 487-497Bonas, U., Anckerveken, G.V., Gene-for-gene interactions: Bacterial avirulence proteins specify plant disease resistance (1999) Curr Opin Plant Biol, 2, pp. 94-98Bonasera, J.M., Kim, J.F., Beer, S.V., PR genes of apple: Identification and expression in response to elicitors and inoculation with Erwinia amylovora (2006) BMC Plant Biol, 6, pp. 23-34Cannon, S.B., May, G.D., Jackson, S.A., Three sequenced legume genomes and many crop species: Rich opportunities for translational genomics (2009) Plant Physiol, 151, pp. 970-977Chester, K.S., The problem of acquired physiological immunity in plants (1933) Quart Rev Phytopathol, 42, pp. 185-209Dafny-Yelin, M., Tzfira, T., Delivery of multiple trans-genes to plant cells (2007) Plant Physiol, 145, pp. 1118-1128Dinesh-Kumar, S.P., Whitham, S., Choi, D., Hehl, R., Corr, C., Baker, B., Transposon tagging of tobacco mosaic virus resistance gene N:I its possible role in the TMV-N-mediated signal transduction pathway (1995) Proc Natl Acad Sci USA, 92, pp. 4175-4180Dixon, M.S., Jones, D.A., Keddie, J.S., Thomas, C.T., Harrison, K., Jones, J.D.G., The tomato Cf2 disease resistance locus comprises two functional genes encoding leucine rich repeats proteins (1996) Cell, 84, pp. 451-459Durrant, W.E., Dong, X., Systemic acquired resistance (2004) Annu Rev Plant Pathol, 42, pp. 185-209Eisen, M.B., Spellman, P.T., Brown, P.O., Botstein, B., Cluster analysis and display of genome-wide expression patterns (1998) Genetics, 25, pp. 14863-14868Ellis, J., Jones, D., Structure and function of proteins controlling strain-specific pathogen resistance in plants (2000) Curr Opin Plant Biol, 1, pp. 288-293Ellis, J., Lawrence, G.J., Finnegan, E.J., Anderson, P.A., Contrasting complexity of two rust resistance loci in flax (1995) Proc Natl Acad Sci USA, 92, pp. 4185-4188Ellis, J., Dodds, P., Pryor, T., Structure, function and evolution of plant disease resistance genes (2000) Curr Opin Plant Biol, 3, pp. 278-284Gaffney, T., Friedrich, L., Vernooij, B., Negrotto, D., Nye, G., Ukness, S., Ward, E., Kessman Hand Ryals, J., Requirementofsalicylic acid for the induction of systemic acquired resistance (1993) Science, 261, pp. 754-756Glombitza, S., Dubuis, P.-H., Thulke, O., Welzl, G., Bovet, L., Götz, M., Affenzeller, M., Asnaghi, C., Crosstalk and differential response to abiotic and biotic stressors reflected at the transcriptional level of effector genes from secondary metabolism (2004) Plant Mol Biol, 54, pp. 817-835Griffith, M., Yaish, M.W.F., Antifreeze proteins in overwintering plants: A tale of two activities (2004) Trends Plant Sci, 9, pp. 399-405Hammond-Kosack, K.E., Jones, J.D.G., Plant disease resistance genes (1997) Annu Rev Plant Physiol, 48, pp. 575-607Hon, W.C., Griffith, M., Mlynarz, A., Kwok, Y.C., Yang, D.S.C., Antifreeze proteins in winter rye are similar to pathogenesis-related proteins (1995) Plant Physiol, 109, pp. 879-889Hulbert, S.H., Webb, C.A., Smith, S.M., Sun, Q., Resistance gene complexes: Evolution and utilization (2001) Annu Rev Phytopathol, 39, pp. 285-312Joahal, G.S., Briggs, S.P., Reductase activity encodes by the Hm1 resistance gene in maize (1992) Science, 198, pp. 985-987Kanazin, V., Marek, L.F., Shoemaker, R.C., Resistance gene analogs are conserved and clustered in soybean (1996) Proc Natl Acad Sci USA, 93, pp. 11746-11750Kido, E.A., Barbosa, P.K., Ferreira Neto, J.C.R., Pandolfi, V., Houllou-Kido, L.M., Crovella, S., Benko-Iseppon, A.M., Identification of plant protein kinases in response to abiotic and biotic stresses using Super SAGE (2011) Curr Prot Pept Sci, 12, pp. 643-656Kitajima, S., Sato, F., Plant pathogenesis-related proteins: Molecular mechanisms of gene expression and protein function (1999) J Biochem, 125, pp. 1-8Lavin, M., Herendeen, P.S., Wojciechowski, M.F., Evolutionary rates analysis of Leguminosae implicates a rapid diversification of lineages during the tertiary (2005) Syst Biol, 54, pp. 575-594Lawrence, G.J., Finnegan, E.J., Ayliffe, M.A., Ellis, J.G., The L6 gene for flax rust resistance is related to the Arabidopsis bacterial resistance gene RPS2 and the tobacco viral resistance gene (1995) N. Plant Cell, 7, pp. 1195-1206Leubner-Metzger, G., β-1,3-glucanase gene expression in low-hydrated seeds as a mechanism for dormancy release during tobacco after-ripening (2005) Plant J, 41, pp. 133-145Li, L., He, H., Zhang, J., Wang, X., Bai, S., Stolc, V., Tongprasit, W., Deng, X.W., Transcriptional analysis of highly syntenic regions between Medicago truncatula and Glycine max using tiling microarrays (2008) Genome Biol, 9, pp. R57Libault, M., Farmer, A., Joshi, T., Takahashi, K., Langley, R.J., Franklin, L.D., He, J., Stacey, G., An integrated transcriptome atlas of the crop model Glycine max and its use in comparative analyses in plants (2010) Plant J, 63, pp. 86-99Liu, B., Zhang, S., Zhu, X., Yang, Q., Wu, S., Mei, M., Mauleon, R., Leung, H., Candidate defense genes as predictors of quantitative blast resistance in rice (2004) Mol Plant Microbe Int, 17, pp. 1146-1152Maisonneuve, B., Bellec, Y., Anderson, P., Michelmore, R.W., Rapid mapping of two genes for resistance to downy mildew from Lactuca serriola to existing clusters of resistance genes (1994) Theor Appl Genet, 89, pp. 96-104Matsumura, H., Kruger, D.H., Kahl, G., Terauchi, R., SuperSAGE: A modern platform for genome-wide quantitative transcript profiling (2008) Curr Pharm Biotechnol, 9, pp. 368-374Melotto, M., Coelho, M.F., Pedrosa-Harand, A., Kelly, J.D., Camargo, L.E., The anthracnose resistance locus Co-4 of common bean is located on chromosome 3 and contains putative disease resistance-related genes (2004) Theor Appl Genet, 109, pp. 690-699Metzler, M.C., Cutt, J.R., Klessig, D.F., Isolation and characterization of a gene encoding a PR-1 like protein from Arabidopsis thaliana (1991) Plant Physiol, 96, pp. 346-348Michelmore, R.W., Meyers, B.C., Clusters of resistance genes in plants evolve by divergent selection and a birth-and-death process (1998) Genome Res, 8, pp. 1113-1130Mindrinos, M., Katagiri, F., Yu, G.L., Ausubel, F.M., The Arabidopsis thaliana disease resistance gene encodes a protein containing a nucleotide-binding site and leucine rich repeats (1994) Cell, 78, pp. 1089-1099Mudge, J., Cannon, S.B., Kalo, P., Oldroyd, G.E., Roe, B.A., Town, C.D., Young, N.D., Highly syntenic regions in the genomes of soybean, Medicago truncatula and Arabidopsis thaliana (2005) BMC Plant Biol, 5, pp. e15Nanda, A.K., Andrio, E., Marino, D., Pauly, N., Dunand, C., Reactive Oxygen Species during plant-microorganism early interactions (2010) J Integr Plant Biol, 52, pp. 195-204Nurnberg, T., Brunner, F., Innate immunity in plants and animals: Emerging parallels between the recognition of general elicitors and pathogen-associated molecular patterns (2002) Curr Opin Plant Biol, 5, pp. 318-324Page, R.D., (1996) Comp Appl Biosci, 12, pp. 357-358Rayapati, P.J., Lee, M., Gregory, J.W., Wise, R.P., A linkage map of diploid Avena based on RFLP loci and a locus conferring resistance to nine isolates of Puccinia coronata var. 'avenae' (1994) Theor Appl Genet, 89, pp. 831-837Salmeron, J.M., Oldroyd, G.E.D., Romens, C.M.T., Scofield, S.R., Kim, H.S., Lavelle, D.T., Dahlbeck, D., Staskawicz, B.J., Tomato Prf is a member of the leucine rich repeats class of plant disease resistance genes and lies embedded within the Pto kinase gene cluster (1996) Cell, 86, pp. 123-133Shoemaker, R.C., Schlueter, J., Doyle, J.J., Paleopolyploidy and gene duplication in soybean and other legumes (2006) Curr Opin Plant Biol, 9, pp. 104-109Song, W.Y., Pi, L.Y., Wang, G.L., Gardner, J., Holsten, T., Ronald, P.C., Evolution of the rice Xa21 disease resistance genes family (1997) Plant Cell, 9, pp. 1279-1287Song, W.Y., Wang, G.L., Kim, H.S., Pi, L.Y., Gardner, J., Wang, B., Holsten, T., Fauquet, C., A receptor kinase-like protein encoded by the rice disease resistance gene Xa21 (1995) Science, 270, pp. 1804-1806Sparla, F., Rotino, L., Valgimigli, M.C., Pupillo, P., Trost, P., Systemic resistance induced by benzothisdizole in pear inoculated with the agent of fire blight (2004) Sci Hortic, 101, pp. 269-279Tamura, K., Dudley, J., Nei, M., Kumar, S., MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) software ver. 4.0 (2007) Mol Biol Evol, 24, pp. 1596-1599Tang, X., Xie, M., Kim, Y.J., Zhou, J., Klessing, D.F., Martin, G.B., Overexpression of Pto activates defense responses and confers broad resistance (1999) Plant Cell, 11, pp. 15-29Thiel, T., Graner, A., Waugh, R., Grosse, I., Close, T.J., Stein, N., Evidence and evolutionary of ancient whole-genome duplication in barley predating the divergence from rice (2009) BMC Evol Biol, 9, pp. 209-227Tornero, P., Gadea, J., Conejero, V., Vera, P., Two PR-1 genes from tomato are differentially regulated and reveal a novel mode of expression for a pathogenesis-related gene during the hypersensitive response and development (1997) Plant Microbe Interact, 10, pp. 624-634Van-Loon, L.C., Geraats, B.P.J., Linthorst, H.J.M., Ethylene as a modulator of disease resistance in plants (2006) Trends Plant Sci, 11, pp. 184-191Van-Loon, L.C., Pierpoint, W.S., Boller, T., Conejero, V., Recommendations for naming plant pathogenesis-related proteins (1999) Plant Mol Biol Rep, 12, pp. 245-264Velazhahan, R., Muthukrishnan, S., Transgenic tobacco plants constitutively overexpressing a rice thaumatin-like protein (PR-5) show enhanced resistance to Alternaria alternata (2003) Plant Biol, 47, pp. 347-354Vergne, E., Grand, X., Ballini, R., Chalvon, V., Saindrenan, P., Tharreau, D., Nottéghem, J.-L., Morel, J.-B., Preformed expression of defense is a hallmark of partial resistance to rice blast fungal pathogen Magnaporthe oryzae (2010) BMC Plant Biol, 10, pp. e206Wanderley-Nogueira, A.C., Mota, N., Lima-Morais, D., Silva, L.C.B., Silva, A.B., Benko-Iseppon, A.M., Abundance and diversity of resistance (R) genes in the sugarcane trans-criptome (2007) Genet Mol Res, 6, pp. 866-889Wang, G.L., Holsten, T.E., Song, W.Y., Wang, H.P., Ronald, P.C., Construction of a rice bacterial artificial chromosome library and identification of clones linked to the Xa21 disease resistance locus (1995) Plant J, 7, pp. 525-533Wendell, J., Genome evolution in polyploids (2000) Plant Mol Biol, 42, pp. 225-249Weng, J.K., Banks, J.A., Chapple, C., Parallels in lignin biosynthesis: A study in Selaginella moellendorffii reveals convergence across 400 million years of evolution (2008) Comm Int Biol, 1, pp. 20-22Wilkstrom, N., Savolainen, V., Chase, M.W., Evolution of the angiosperms: Calibrating the family tree (2001) Proc Soc Biol Sci, 268, pp. 2211-2220Zeier, J., Pink, B., Mueller, M.J., Berger, S., Light conditions influence specific defense responses in incompatible plant-pathogen interactions: Uncoupling systemic resistance from salicylic acid and PR-1 accumulation (2004) Planta, 219, pp. 673-68

Proteomic characterization and biological activities of the mucus produced by the zoanthid Palythoa caribaeorum (Duchassaing & Michelotti, 1860)

Abstract Mucus, produced by Palythoa caribaeorum has been popularly reported due to healing, anti-inflammatory, and analgesic effects. However, biochemical and pharmacological properties of this mucus remains unexplored. Therefore, the present study aimed to study its proteome profile by 2DE electrophoresis and MALDI-TOF. Furthermore, it was evaluated the cytotoxic, antibacterial, and antioxidant activities of the mucus and from its protein extract (PE). Proteomics study identified14 proteins including proteins involved in the process of tissue regeneration and death of tumor cells. The PE exhibited cell viability below 50% in the MCF-7 and S-180 strains. It showed IC50 of 6.9 μg/mL for the J774 lineage, and also, favored the cellular growth of fibroblasts. Furthermore, PE revealed activity against Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, and Staphylococcus epidermidis (MIC of 250 μg/mL). These findings revealed the mucus produced by Palythoa caribaeorum with biological activities, offering alternative therapies for the treatment of cancer and as a potential antibacterial agent

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC

Measurements of inclusive jet suppression in heavy ion collisions at the LHC provide direct sensitivity to the physics of jet quenching. In a sample of lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the anti-kt algorithm with values for the distance parameter that determines the nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp. Jet production is found to be suppressed by approximately a factor of two in the 10% most central collisions relative to peripheral collisions. Rcp varies smoothly with centrality as characterized by the number of participating nucleons. The observed suppression is only weakly dependent on jet radius and transverse momentum. These results provide the first direct measurement of inclusive jet suppression in heavy ion collisions and complement previous measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables, submitted to Physics Letters B. All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02

Suplementos para ovinos mantidos em pastos de capim-marandu

O objetivo deste trabalho foi avaliar o efeito da suplementação na resposta produtiva, no pH e no nitrogênio amoniacal ruminal, e no custo de produção de ovinos em pastagem de capim-marandu no período da seca. O experimento teve a duração de 84 dias. Utilizaram-se 20 cordeiros não castrados com idade e peso corporal inicial médios de quatro meses e 24,20 kg, respectivamente, para avaliação do desenvolvimento, distribuídos em cada um dos tratamentos que são os suplementos, mineral, energético, proteico e múltiplo, com cinco animais por tatamento, em área de 0,1 ha. Para avaliação dos parâmetros nutricionais, foram utilizados quatro ovinos fistulados no rúmen com 12 meses e 55 kg de peso corporal foram distribuídos em quatro piquetes de 0,1 ha. Avaliaram-se os suplementos mineral, energético, múltiplo e proteico. Os ganhos de peso foram de 0,017, -0,008, 0,024 e 0,077 kg por dia para os suplementos mineral, energético, múltiplo e proteico, respectivamente. Quatro horas após suplementação, os valores de pH ruminal foram de 6,30, 6,40, 6,18 e 6,24 para os suplementos mineral, energético, múltiplo e proteico, respectivamente. Os valores para nitrogênio amoniacal do líquido ruminal foram de 10,57, 7,36, 21,58 e 24,50 mg dL-1 para os suplementos mineral, energético, múltiplo e proteico, respectivamente. Os suplementos mineral e proteico produziram o ganho de peso com o menor custo. O uso de suplemento energético para cordeiros submetidos à forragem com baixo teor de proteína reduz o ganho de peso

Salt stress induced damages on the photosynthesis of physic nut young plants

Salinity is a major limiting factor to crop productivity in the world especially in semiarid regions. The aim of this study was to evaluate the photosynthetic resistance of Jatropha curcas (L.) young plants subjected to salt stress. The experiment was carried out in a completely randomized design with treatments in a 2 x 3 factorial: two NaCl levels (0 and 100 mmol L-1) and three harvest times: 7 and 14 days of salt exposure and three days of recovery. Leaf Na+ and Cl-concentrations and the K+/Na+ ratios, after seven days of salt exposure, did not reach ionic toxic levels, suggesting that the NaCl-induced osmotic effects prevailed over the ionic ones. Under this condition, the salt stress caused reduction in leaf gas exchange parameters, such as CO2 fixation, stomatal conductance and transpiration. In contrast, salt stress did not change the photochemical efficiency of photossystem II. Conversely, after 14 days of treatment, Na+ and Clions reached very high concentrations, up to toxic levels in leaves. Under such conditions, both leaf gas exchange and photochemistry suffered strong impairment probably caused by ionic toxicity. The recovery treatment for 3d did not significantly decrease the leaf salt concentrations and no improvement was observed in the photosynthetic performance. Physic nut young plants are sensitive to high NaCl-salinity conditions, with high leaf Na+ and Cl- concentrations, low K+/Na+ ratio and great photosynthetic damages due to stomatal and biochemical limitations.A salinidade é um dos principais fatores que limitam a produtividade das culturas no mundo principalmente em regiões semiáridas. Avaliou-se a resistência da fotossíntese de plantas jovens de pinhãomanso (Jatropha curcas L.) submetidas ao estresse salino. O experimento foi realizado em delineamento inteiramente casualizado com tratamentos em fatorial 2 x 3: duas concentrações de NaCl (0 e 100 mmol L-1) e três tempos de avaliação (7 e 14 dias de exposição e três dias de recuperação). As concentrações de Na+ e Cl- e a relação K+/Na+ nas folhas, após sete dias de exposição ao sal, não indicaram níveis tóxicos, sugerindo os efeitos osmóticos induzidos pelo NaCl prevaleceram sobre as causas iônicas. Sob essas condições, o estresse salino causou redução nos parâmetros de trocas gasosas, como fixação de CO2, condutância estomática e transpiração, mas ao contrário, não alterou a eficiência fotoquímica do fotossistema II. Após 14 dias de tratamento, os íons salinos atingiram concentrações muito elevadas nas folhas, provavelmente atingindo níveis tóxicos. Em tais condições, as trocas gasosas e a atividade fotoquímica sofreram forte redução causada pelo estresse iônico. O tratamento de recuperação não induziu queda intensa nas concentrações dos íons salinos nas folhas e nenhuma melhoria foi observada no desempenho fotossintético. Plantas jovens de pinhão manso são sensíveis a condições de salinidade elevada por NaCl, mostrando altas concentrações de Na+ e Cl-, baixa razão K+/Na+ e danos fotossintéticos intensos causados tanto por limitações estomáticas como por limitações bioquímicas

Physical activity attenuates the influence of FTO variants on obesity risk: A meta-analysis of 218,166 adults and 19,268 children

Background: The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n = 218,166) and nine studies of children and adolescents (n = 19,268). Methods and Findings: All studies identified to have data on the FTO rs9939609 variant (or any proxy [r2>0.8]) and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were performed within each study by including the FTO×PA interaction term in an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction terms. In adults, the minor (A-) allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20-1.26), but PA attenuated this effect (pinteraction= 0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio = 1.22/allele, 95% CI 1.19-1.25) than in the inactive group (odds ratio = 1.30/allele, 95% CI 1.24-1.36). No such interaction was found in children and adolescents. Concl