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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
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Disease relevance of Europe


Psychiatry related information on Europe


High impact information on Europe

  • Two MYH missense mutations, Y165C and G382D, already found to be frequent among patients from northern Europe, were also preponderant in our survey [7].
  • BACKGROUND: The highest incidence of osteoporotic fractures is found in northern Europe, where dietary intake of vitamin A (retinol) is unusually high [8].
  • Analysis of haplotypes associated with the deletion revealed a founder effect in Ashkenazi Jews and also suggested a common founder for countries in Western Europe. These results have important implications for the diagnosis and counseling of families with DFNB1 deafness [9].
  • The existence of patients with clinical and histological features of HH, but without mutations in HLA-H gene, suggests that in Italy the disease is more heterogeneous than reported in northern Europe [10].
  • Mutational spectrum of phenylalanine hydroxylase deficiency in Sicily: implications for diagnosis of hyperphenylalaninemia in southern Europe [11].

Chemical compound and disease context of Europe


Biological context of Europe

  • The association between the HLA class II DR15, DQ6, Dw2 haplotype and MS has been well documented in patients with ancestral origins in Northern Europe. Conversely, linkage analysis of this region in multiplex families, derived from a population base, has generated negative results [17].
  • Our data further suggest that allelic variation in cagA may exist and that distinct H. pylori genotypes may circulate in China and Western Europe [18].
  • We have studied the linkage disequilibrium between these markers and the CF mutations, the probable number of independent secondary CFX (non-delta F508) mutations, and the genetic differences between Spain and Western Europe [19].
  • However, the prevalence of atopy is lower in children in central and Eastern Europe, where air pollution poses a major problem, than in Western Europe. Indeed, preliminary data from the International Study of Asthma and Allergy in Children (ISAAC) confirm that the prevalence of childhood atopy is lower in Eastern Europe than in Scandinavia [20].
  • This resistance pattern correlates with patterns reported recently for Central and Southern Europe. Due to dissemination of plasmids coding for the AAC(3)-II enzyme, the majority of Czechoslovak gentamicin-resistant Gram-negative strains were also tobramycin- (87%) and netilmicin-resistant (68%) [21].

Anatomical context of Europe

  • This and other genetic risk factors might actually be a surrogate for the distinct geographic distribution of the disease with a marked preference for Northern Europe. Studies on functional aspects of T cells accumulating in the vasculitic foci have demonstrated a strong bias for Th1 helper T cells which locally release IL-2 and IFN-gamma [22].
  • Susceptibility to celiac disease in Northern Europe is associated with the human leukocyte antigens (HLA) B8, DR3 and DQ2, which exist together on an extended haplotype [23].

Associations of Europe with chemical compounds

  • For unknown reasons, the highest incidence of osteoporosis is found in northern Europe. In these populations, the sunlight exposure is limited and the vitamin A intake is high [24].
  • The aim of this study was to detect the prevalence of low serum 25-hydroxyvitamin D [S-25(OH)D] and elevated serum intact parathyroid hormone (S-iPTH) concentrations in healthy young adults in the winter in northern Europe and to characterize the determinants of these variables [25].
  • Many studies have been undertaken both in this country and in western Europe to determine the clinical effectiveness of ceftazidime in seriously ill patients [26].
  • This finding contrasts with the hypothesis of a continuous increase in frequency of lactose malabsorption from northern to southern Europe and is probably due to the complex genetic history of the Italian population [27].
  • Differences in glucose-dependent insulinotrophic polypeptide hormone and hepatic lipase in subjects of southern and northern Europe: implications for postprandial lipemia [28].

Gene context of Europe

  • CONCLUSIONS: Our results indicate that polymorphism in the GSTM3 may be an important biomarker for PC risk, especially in the definition of the genetic risk profile of populations of southern Europe [29].
  • In Northern Europe, more than 90% of HH patients are homozygous for a mis-sense mutation (C282Y) in the HFE1 gene product [30].
  • More than 80 mutations of the PKD1 gene have been reported, mostly in patients from Western Europe. New techniques are being used to detect an increasing number of mutations, even in the homologous region of the PKD1 gene [31].
  • An ethnic influence on the distribution of mutations was confirmed: T216M in SLC3A1 is the major mutation in south-eastern Europe, whereas M467T in SLC3A1 is mainly found in western Europe. A complex duplication in SLC3A1 is restricted to German patients [32].
  • Tau (MAPT) mutation Arg406Trp presenting clinically with Alzheimer disease does not share a common founder in Western Europe [33].

Analytical, diagnostic and therapeutic context of Europe


  1. Variegate porphyria in Western Europe: identification of PPOX gene mutations in 104 families, extent of allelic heterogeneity, and absence of correlation between phenotype and type of mutation. Whatley, S.D., Puy, H., Morgan, R.R., Robreau, A.M., Roberts, A.G., Nordmann, Y., Elder, G.H., Deybach, J.C. Am. J. Hum. Genet. (1999) [Pubmed]
  2. Using phylogenetic analysis to trace HIV-1 migration among western European injecting drug users seroconverting from 1984 to 1997. Op de Coul, E.L., Prins, M., Cornelissen, M., van der Schoot, A., Boufassa, F., Brettle, R.P., Hernández-Aguado, L., Schiffer, V., McMenamin, J., Rezza, G., Robertson, R., Zangerle, R., Goudsmit, J., Coutinho, R.A., Lukashov, V.V. AIDS (2001) [Pubmed]
  3. Tissue stores of individual monounsaturated fatty acids and breast cancer: the EURAMIC study. European Community Multicenter Study on Antioxidants, Myocardial Infarction, and Breast Cancer. Simonsen, N.R., Fernandez-Crehuet Navajas, J., Martin-Moreno, J.M., Strain, J.J., Huttunen, J.K., Martin, B.C., Thamm, M., Kardinaal, A.F., van't Veer, P., Kok, F.J., Kohlmeier, L. Am. J. Clin. Nutr. (1998) [Pubmed]
  4. A common ancestral glycoprotein (GP) 9 1828A>G (Asn45Ser) gene mutation occurring in European families from Australia and Northern Europe with Bernard-Soulier Syndrome (BSS). Liang, H.P., Morel-Kopp, M.C., Clemetson, J.M., Clemetson, K.J., Kekomaki, R., Kroll, H., Michaelides, K., Tuddenham, E.G., Vanhoorelbeke, K., Ward, C.M. Thromb. Haemost. (2005) [Pubmed]
  5. TP53 mutations, amplification of P63 and expression of cell cycle proteins in squamous cell carcinoma of the oesophagus from a low incidence area in Western Europe. Tanière, P., Martel-Planche, G., Saurin, J.C., Lombard-Bohas, C., Berger, F., Scoazec, J.Y., Hainaut, P. Br. J. Cancer (2001) [Pubmed]
  6. Decreased frequency of apolipoprotein E epsilon4 allele from Northern to Southern Europe in Alzheimer's disease patients and centenarians. Panza, F., Solfrizzi, V., Torres, F., Mastroianni, F., Del Parigi, A., Colacicco, A.M., Basile, A.M., Capurso, C., Noya, R., Capurso, A. Neurosci. Lett. (1999) [Pubmed]
  7. High frequency of MYH gene mutations in a subset of patients with familial adenomatous polyposis. Venesio, T., Molatore, S., Cattaneo, F., Arrigoni, A., Risio, M., Ranzani, G.N. Gastroenterology (2004) [Pubmed]
  8. Excessive dietary intake of vitamin A is associated with reduced bone mineral density and increased risk for hip fracture. Melhus, H., Michaëlsson, K., Kindmark, A., Bergström, R., Holmberg, L., Mallmin, H., Wolk, A., Ljunghall, S. Ann. Intern. Med. (1998) [Pubmed]
  9. Prevalence and evolutionary origins of the del(GJB6-D13S1830) mutation in the DFNB1 locus in hearing-impaired subjects: a multicenter study. Del Castillo, I., Moreno-Pelayo, M.A., Del Castillo, F.J., Brownstein, Z., Marlin, S., Adina, Q., Cockburn, D.J., Pandya, A., Siemering, K.R., Chamberlin, G.P., Ballana, E., Wuyts, W., Maciel-Guerra, A.T., Alvarez, A., Villamar, M., Shohat, M., Abeliovich, D., Dahl, H.H., Estivill, X., Gasparini, P., Hutchin, T., Nance, W.E., Sartorato, E.L., Smith, R.J., Van Camp, G., Avraham, K.B., Petit, C., Moreno, F. Am. J. Hum. Genet. (2003) [Pubmed]
  10. Mutation analysis of the HLA-H gene in Italian hemochromatosis patients. Carella, M., D'Ambrosio, L., Totaro, A., Grifa, A., Valentino, M.A., Piperno, A., Girelli, D., Roetto, A., Franco, B., Gasparini, P., Camaschella, C. Am. J. Hum. Genet. (1997) [Pubmed]
  11. Mutational spectrum of phenylalanine hydroxylase deficiency in Sicily: implications for diagnosis of hyperphenylalaninemia in southern Europe. Guldberg, P., Romano, V., Ceratto, N., Bosco, P., Ciuna, M., Indelicato, A., Mollica, F., Meli, C., Giovannini, M., Riva, E. Hum. Mol. Genet. (1993) [Pubmed]
  12. The OPTAMA programme: utilizing MYSTIC (2002) to predict critical pharmacodynamic target attainment against nosocomial pathogens in Europe. Masterton, R.G., Kuti, J.L., Turner, P.J., Nicolau, D.P. J. Antimicrob. Chemother. (2005) [Pubmed]
  13. Antibody profiles and self-reported symptoms to pollen-related food allergens in grass pollen-allergic patients from northern Europe. Ghunaim, N., Grönlund, H., Kronqvist, M., Grönneberg, R., Söderström, L., Ahlstedt, S., van Hage-Hamsten, M. Allergy (2005) [Pubmed]
  14. Systemic therapy with fumaric acid derivates: new possibilities in the treatment of psoriasis. Nieboer, C., de Hoop, D., van Loenen, A.C., Langendijk, P.N., van Dijk, E. J. Am. Acad. Dermatol. (1989) [Pubmed]
  15. Glycaemic effects of traditional European plant treatments for diabetes. Studies in normal and streptozotocin diabetic mice. Swanston-Flatt, S.K., Day, C., Flatt, P.R., Gould, B.J., Bailey, C.J. Diabetes Res. (1989) [Pubmed]
  16. Management of inflammatory bowel diseases in Eastern Europe. Lakatos, L., Lakatos, P.L. Postgraduate medical journal. (2006) [Pubmed]
  17. Multiple sclerosis and the HLA-D region: linkage and association studies. Kellar-Wood, H.F., Wood, N.W., Holmans, P., Clayton, D., Robertson, N., Compston, D.A. J. Neuroimmunol. (1995) [Pubmed]
  18. Equally high prevalences of infection with cagA-positive Helicobacter pylori in Chinese patients with peptic ulcer disease and those with chronic gastritis-associated dyspepsia. Pan, Z.J., van der Hulst, R.W., Feller, M., Xiao, S.D., Tytgat, G.N., Dankert, J., van der Ende, A. J. Clin. Microbiol. (1997) [Pubmed]
  19. Genotyping of the Spanish cystic fibrosis population at the delta F508 mutation site and RFLP linked loci. Jaume-Roig, B., Simon-Bouy, B., Taillandier, A., Serre, J.L., Antich, J., Bellon, J., Boué, J., Boué, A. Hum. Genet. (1990) [Pubmed]
  20. Epidemiology of pollution-induced airway disease in Scandinavia and Eastern Europe. Björkstén, B. Allergy (1997) [Pubmed]
  21. Development of gentamicin resistance in gram-negative bacteria in Czechoslovakia and correlation with its usage. Kettner, M., Krćméry, V. Drugs under experimental and clinical research. (1988) [Pubmed]
  22. The pathogenic role of T lymphocytes in vasculitis. Weyand, C.M., Goronzy, J.J. Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG / World Association of Sarcoidosis and Other Granulomatous Disorders. (1996) [Pubmed]
  23. HLA class II alleles associated with celiac disease susceptibility in a southern European population. Tighe, M.R., Hall, M.A., Barbado, M., Cardi, E., Welsh, K.I., Ciclitira, P.J. Tissue Antigens (1992) [Pubmed]
  24. Vitamin A antagonizes calcium response to vitamin D in man. Johansson, S., Melhus, H. J. Bone Miner. Res. (2001) [Pubmed]
  25. Vitamin D deficiency and bone health in healthy adults in Finland: could this be a concern in other parts of Europe? Lamberg-Allardt, C.J., Outila, T.A., Kärkkainen, M.U., Rita, H.J., Valsta, L.M. J. Bone Miner. Res. (2001) [Pubmed]
  26. Ceftazidime in the treatment of nosocomial sepsis. Young, L.S. Am. J. Med. (1985) [Pubmed]
  27. Primary adult lactose malabsorption in Italy: regional differences in prevalence and relationship to lactose intolerance and milk consumption. Cavalli-Sforza, L.T., Strata, A., Barone, A., Cucurachi, L. Am. J. Clin. Nutr. (1987) [Pubmed]
  28. Differences in glucose-dependent insulinotrophic polypeptide hormone and hepatic lipase in subjects of southern and northern Europe: implications for postprandial lipemia. Jackson, K.G., Zampelas, A., Knapper, J.M., Roche, H.M., Gibney, M.J., Kafatos, A., Gould, B.J., Wright, J.W., Williams, C.M. Am. J. Clin. Nutr. (2000) [Pubmed]
  29. Metabolic susceptibility genes and prostate cancer risk in a southern European population: the role of glutathione S-transferases GSTM1, GSTM3, and GSTT1 genetic polymorphisms. Medeiros, R., Vasconcelos, A., Costa, S., Pinto, D., Ferreira, P., Lobo, F., Morais, A., Oliveira, J., Lopes, C. Prostate (2004) [Pubmed]
  30. Over-expression of wild-type and mutant HFE in a human melanocytic cell line reveals an intracellular bridge between MHC class I pathway and transferrin iron uptake. Fergelot, P., Orhant, M., Thénié, A., Loyer, P., Ropert-Bouchet, M., Lohyer, S., Le Gall, J.Y., Mosser, J. Biol. Cell (2003) [Pubmed]
  31. Mutations of the PKD1 gene among Japanese autosomal dominant polycystic kidney disease patients, including one heterozygous mutation identified in members of the same family. Mizoguchi, M., Tamura, T., Yamaki, A., Higashihara, E., Shimizu, Y. J. Hum. Genet. (2001) [Pubmed]
  32. The population-specific distribution and frequencies of genomic variants in the SLC3A1 and SLC7A9 genes and their application in molecular genetic testing of cystinuria. Schmidt, C., Vester, U., Hesse, A., Lahme, S., Lang, F., Zerres, K., Eggermann, T. Urol. Res. (2004) [Pubmed]
  33. Tau (MAPT) mutation Arg406Trp presenting clinically with Alzheimer disease does not share a common founder in Western Europe. Rademakers, R., Dermaut, B., Peeters, K., Cruts, M., Heutink, P., Goate, A., Van Broeckhoven, C. Hum. Mutat. (2003) [Pubmed]
  34. A global study of vitamin D status and parathyroid function in postmenopausal women with osteoporosis: baseline data from the multiple outcomes of raloxifene evaluation clinical trial. Lips, P., Duong, T., Oleksik, A., Black, D., Cummings, S., Cox, D., Nickelsen, T. J. Clin. Endocrinol. Metab. (2001) [Pubmed]
  35. No association between Helicobacter pylori genotypes and antibiotic resistance phenotypes within families. Zschausch, H.C., Han, S.R., Meyer, H.G., Maeurer, M.J. Helicobacter (2002) [Pubmed]
  36. Clinical interventions in diabetic renal disease. Leese, G.P., Vora, J.P. Curr. Opin. Nephrol. Hypertens. (1995) [Pubmed]
  37. Hepatitis C virus genotyping by means of 5'-UR/core line probe assays and molecular analysis of untypeable samples. Stuyver, L., Wyseur, A., van Arnhem, W., Lunel, F., Laurent-Puig, P., Pawlotsky, J.M., Kleter, B., Bassit, L., Nkengasong, J., van Doorn, L.J. Virus Res. (1995) [Pubmed]
  38. Technology evaluation: omalizumab, Genentech/Novartis/Tanox. Lazaar, A.L. Curr. Opin. Mol. Ther. (2003) [Pubmed]
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