Karla Köpke

Robert Koch Institut, Berlín, Berlin, Germany

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Publications (24)125.21 Total impact

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    ABSTRACT: THE NUMBER OF PATIENTS SEEKING HEALTH CARE IS A CENTRAL INDICATOR THAT MAY SERVE SEVERAL DIFFERENT PURPOSES: (1) as a proxy for the impact on the burden of the primary care system; (2) as a starting point to estimate the number of persons ill with influenza; (3) as the denominator data for the calculation of case fatality rate and the proportion hospitalized (severity indicators); (4) for economic calculations. In addition, reliable estimates of burden of disease and on the health care system are essential to communicate the impact of influenza to health care professionals, public health professionals and to the public. Using German syndromic surveillance data, we have developed a novel approach to describe the seasonal variation of medically attended acute respiratory infections (MAARI) and estimate the excess MAARI attributable to influenza. The weekly excess inside a period of influenza circulation is estimated as the difference between the actual MAARI and a MAARI-baseline, which is established using a cyclic regression model for counts. As a result, we estimated the highest ARI burden within the last 10 years for the influenza season 2004/05 with an excess of 7.5 million outpatient visits (CI95% 6.8-8.0). In contrast, the pandemic wave 2009 accounted for one third of this burden with an excess of 2.4 million (CI95% 1.9-2.8). Estimates can be produced for different age groups, different geographic regions in Germany and also in real time during the influenza waves.
    PLoS ONE 07/2013; 8(7):e64593. DOI:10.1371/journal.pone.0064593 · 3.53 Impact Factor
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    S Buda, K Köpke, W Haas
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    ABSTRACT: The aim of the investigation is the descriptive analysis of case-based information from mandatory notifications in the first year of the influenza pandemic (H1N1) 2009 in order to identify and describe epidemiological characteristics and risk factors for severe outcome. Four distinct time periods were defined to describe the age distribution of hospitalized and fatal cases. In contrast, stratified (age, sex) analysis of risk factors was carried out for the whole time period of pandemic influenza activity (notification weeks 18/2009 to 17/2010). Characteristic differences in the age distribution of reported cases were observed according to the time period. Among the reported risk factors, immunosuppression exhibited the highest probability for hospitalization or a fatal outcome (OR=8.82; CI95% 7.3-10.6 and OR=37.4; CI95% 25.5-54.8, respectively). The stratified analysis showed that this was especially pronounced for patients in the age group 60 years and above. Single case-based notifications of pandemic influenza have proven to be an invaluable source of information for assessing the epidemiological characteristics of the influenza pandemic 2009 in Germany. In addition, it allows comparative analysis of certain risk groups for severe disease. The information, thus, provides an important contribution for further developing and improving of public health recommendations.
    Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz 12/2010; 53(12):1223-30. DOI:10.1007/s00103-010-1158-0 · 1.01 Impact Factor
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    ABSTRACT: Die Ergebnisse der Influenza-Überwachung der Saison 2009/10 basieren auf den Daten des Sentinelsystems der Arbeitsgemeinschaft Influenza (AGI) des Robert Koch-Instituts (RKI) zum Auftreten akuter Atemwegserkrankungen in primärversorgenden Praxen. Die Ergebnisse fußen auch auf Informationen über die virologische Analyse der Influenzaviren von Patienten mit Influenza-typischen Symptomen. In dieser Saison trug die Kooperation mit den Landeslaboren in Bayern, Mecklenburg- Vorpommern, Sachsen und erstmals auch Sachsen-Anhalt zu einer Verstärkung der virologischen Surveillance in diesen Bundesländern bei. Zusätzlich werden erste Ergebnisse des Sentinels zur elektronischen Erfassung von Diagnosecodes akuter respiratorischer Erkrankungen (SEEDARE) vorgestellt. In diesem Bericht berücksichtigt wurden weiterhin die nach dem Infektionsschutzgesetz (IfSG) von den deutschen Gesundheitsämtern erhobenen Meldedaten zu Influenza-Erkrankungen aus dem gesamten Bundesgebiet sowie Daten aus Studien des RKI im Rahmen der Influenzapandemie A (H1N1) 2009. Die Auswertung für diesen Bericht erfolgte aus den Daten für den Zeitraum von der 16. Kalenderwoche (KW) 2009 bis zur 15. KW 2010. Obwohl seit Ende April 2009 laborbestätigte Fälle von pandemischer Influenza A (H1N1) 2009 gemeldet wurden, deren Anzahl bis Anfang August zunächst anstieg, konnte ein epidemiologisch messbarer Einfluss auf die Morbidität der Bevölkerung an akuten Atemwegserkrankungen erst ab der 42. KW beobachtet werden. Die in dieser und den folgenden Wochen beobachtete Influenza-Aktivität war stark erhöht. Die pandemische Influenzawelle dauerte insgesamt von der 42. KW 2009 bis zur 2. KW 2010 an. Die Anzahl der während der Influenzawelle geschätzten Exzess-Konsultationen betrug 2.930.000 (95 %-Konfidenzintervall 2.510.000 – 3.360.000). Dieser Wert liegt im Bereich einer üblichen saisonalen Influenzawelle, war jedoch niedriger als in der Saison 2008/09. Influenza-assoziierte Arbeitsunfähigkeiten (bzw. Pflegebedürftigkeit bei Kindern und älteren Menschen über 60 Jahre) wurden auf 1.547.000 (95 %-Konfidenzintervall 528.000 – 2.574.000) geschätzt. Die geschätzte Anzahl der grippebedingten zusätzlichen Krankenhauseinweisungen betrug 5.300 (95 %-Konfidenzintervall 1.400 – 9.300). Eine Berechnung der Übersterblichkeit während der Influenzawelle konnte noch nicht durchgeführt werden, da endgültige Zahlen der Todesfallstatistik zum Zeitpunkt der Fertigstellung des Berichts erst bis zum Jahr 2008 vorlagen. Im Nationalen Referenzzentrum für Influenza (NRZ) wurden pandemische A (H1N1)-Viren seit ihrem ersten Auftreten in Deutschland im April 2009 über die nächsten drei Monate häufiger, danach im Sommer jedoch eher sporadisch nachgewiesen. In den ersten Oktoberwochen vermehrten sich die Nachweise und lagen über denen vom September. Mitte Oktober (43. KW) stiegen sie auf das Dreifache an und zeigten mit einem weiteren drastischen Anstieg in der 44. KW die begonnene Influenzawelle an. Im AGI-Sentinel wurden die meisten pandemischen A (H1N1)-Viren zwischen der 45. und 48. KW identifiziert. Im Gegensatz zur saisonalen Influenza wurden auch noch viele Wochen nach Abklingen der Welle Influenzaviren nachgewiesen. Der letzte Nachweis im Sentinel stammt aus der 12. KW. Die antigenetische Analyse zeigt, dass alle bisher isolierten pandemischen A (H1N1)-Viren dem Stamm A/California/7/2009 sehr ähnlich sind. Die nur sehr sporadisch aufgetretenen Influenza A (H3N2)-Viren reagierten sehr gut mit dem Antiserum gegen den neuen Referenzstamm A/Perth/16/2009. Die wenigen identifizierten Influenza B-Viren stammten aus der Victoria-Linie und wiesen antigenetisch eine große Ähnlichkeit mit der Influenza B-Komponente des Impfstoffs für die Saison 2009/10 auf. Für die Saison 2010/11 gab die Weltgesundheitsorganisation (WHO) folgende Empfehlung für die Impfstoffzusammensetzung in der Nördlichen Hemisphäre bekannt: ▶ Influenza A (H1N1)-Komponente: ein A/California/ 7/2009 (H1N1)-ähnliches Virus; dies ist die Komponente für das pandemische Influenzavirus A (H1N1) 2009 ▶ Influenza A (H3N2)-Komponente: ein A/Perth/ 16/2009 (H3N2)-ähnliches Virus; die Komponente der Vorsaison wurde ausgetauscht ▶ Influenza B-Komponente: ein B/Brisbane/ 60/2008-ähnliches Virus aus der Victoria-Linie; diese Komponente wurde aus der Vorsaison beibehalten
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    ABSTRACT: Little was known about the sequence variability of the human Arrestin domain-containing 4 gene (ARRDC4). We sequenced its DNA from exon 2 to exon 8 in a sample of 92 Russians. Seven variants were identified; one of them has not been described yet. It causes an amino acid change from Thr to Met. Identified variants were genotyped in the complete sample of 253 unrelated men and women to analyze haplotype distribution. Fifteen haplotypes were inferred. Nine haplotypes had estimated frequencies > 1%. Ninety-five percent of all haplotypes were determined by five haplotype-tagging single nucleotide polymorphisms. Haplotypes form two clades. The two most common haplotypes cover 76% of all haplotypes. The certainty of the haplotype reconstruction does not depend on the haplotype-inferring algorithms, but is a result of the anomalous haplotype distribution of ARRDC4, which makes this gene a suitable candidate gene for haplotype association studies. Interestingly, there is a great evolutionary distance between the two most common haplotypes, which could suggest a more complicated coalescent process with either past gene flow, selections, or bottlenecks.
    Genetic Testing 03/2008; 12(1):147-52. DOI:10.1089/gte.2007.0049 · 1.65 Impact Factor
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    ABSTRACT: OATP1B1 is one of the key hepatocellular uptake transporters providing extraction of diverse compounds, including bile acids, xenobiotics, and a variety of drugs, from portal venous blood into the liver. Polymorphisms of the SLCO1B1 gene have been demonstrated to influence in vitro transport function and the pharmacokinetic profile of compounds. The goal of our study was the comparison of SLCO1B1 gene sequence variability in three ethnic groups as a basis for future genetic association studies. Eighteen exonic SLCO1B1 single nucleotide polymorphisms (SNPs) were genotyped by PCR and RFLP analysis in 300 German, 94 Turkish, and 115 African subjects. Calculation of pairwise linkage disequilibrium and estimation of population haplotype frequencies were carried out, and haplotype block structure was determined. Only eight genotyped SNPs (c.388A>G, c.411G>A, c.463C>A, c.521T>C, c.571C>T, c.597C>T, c.1463G>C, c.1929A>C) were found in at least one of our German, Turkish, or African samples. A total of 12 haplotypes with a frequency >or=1% in at least one of the three populations could be inferred. Between the Caucasian and African samples, significant differences in sequence variability were observed leading to a different haplotype profile in these populations. Our results demonstrate a high sequence variability of OATP1B1 within different popuations. In the future, distinct haplotypes should be taken into account when studying the effect of OATP1B1 on drugs in different populations.
    European Journal of Clinical Pharmacology 03/2008; 64(3):257-66. DOI:10.1007/s00228-007-0409-y · 2.70 Impact Factor
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    ABSTRACT: The role of the single nucleotide polymorphisms (SNPs) on positions 2677G>T/A and 3435C>T of the multi-drug-resistance gene 1 (MDR1) in inflammatory bowel disease (IBD) remains unclear. To further elucidate the potential impact of MDR1 two-locus genotypes on susceptibility to IBD and disease behaviour. Three hundred eighty-eight German IBD patients [244 with Crohn's disease (CD), 144 with ulcerative colitis (UC)] and 1,005 German healthy controls were genotyped for the two MDR1 SNPs on positions 2677G>T/A and 3435C>T. Genotype-phenotype analysis was performed with respect to disease susceptibility stratified by age at diagnosis as well as disease localisation and behaviour. Genotype distribution did not differ between all UC or CD patients and controls. Between UC and CD patients, however, we observed a trend of different distribution of the combined genotypes derived from SNPs 2677 and 3435 (chi(2) = 15.997, df = 8, p = 0.054). In subgroup analysis, genotype frequencies between UC patients with early onset of disease and controls showed significant difference for combined positions 2677 and 3435 (chi(2) = 16.054, df = 8, p = 0.034 for age at diagnosis >or=25, lower quartile). Herein the rare genotype 2677GG/3435TT was more frequently observed (odds ratio = 7.0, 95% confidence interval 2.5 - 19.7). In this group severe course of disease behaviour depended on the combined MDR1 SNPs (chi(2) = 16.101, df = 6, p = 0.017 for age at diagnosis >or=25). No association of MDR1 genotypes with disease subgroups in CD was observed. While overall genotype distribution did not differ, combined MDR1 genotypes derived from positions 2677 and 3435 are possibly associated with young age onset of UC and severe course of disease in this patient group.
    European Journal of Clinical Pharmacology 10/2007; 63(10):917-25. DOI:10.1007/s00228-007-0334-0 · 2.70 Impact Factor
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    ABSTRACT: The multidrug resistance gene 1 (MDR1) seems to play a role in the carcinogenesis of colorectal tumors. The importance of MDR1 SNPs 2677G > T/A in exon 21 and 3435C > T in exon 26 for cancer susceptibility, however, has not yet been clearly defined. Two hundred and eighty-five colorectal cancer patients and 275 controls from five hospitals in the European part of Russia were genotyped for the polymorphisms -129T > C (rs3213619) in exon 1b, 2677G > T/A (rs2032582), and 3435C > T (rs1045642) in this population-based case-control study. Genotype-phenotype analysis was performed with simultaneous consideration of lifestyle risk factors. Our analysis confirmed the preponderate impact of smoking on colorectal cancer development. The risk of heavy smokers (>/=60 pack years) to develop colorectal cancer by far exceeded that of lifelong non-smokers (OR = 3.9, 95% CI: 1.4 to 10.6). Smoking is a more potent risk factor than is the genetic influence of MDR1 in our study. However, a smoking and age-stratified analysis, revealed a statistically significant association between MDR1 genotypes and colorectal cancer in life-long non-smokers with an age > or =63 years (the median age in our sample). The association was stronger for rectal cancer than for colon cancer. Patients who carried the genotypes (-129TT; 2677GG; 3435CC) or (-129TT; 2677TT; 3435TT) developed more frequently colorectal cancer than others (OR = 3.9; 95% CI: 2.0 to 7.7). Our results show that the interaction of genetic and lifestyle risk factors should be taken into account to elucidate the genetic influence of MDR1 variability on cancer susceptibility.
    European Journal of Clinical Pharmacology 01/2007; 63(1):9-16. DOI:10.1007/s00228-006-0225-9 · 2.70 Impact Factor
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    ABSTRACT: We analyzed allele frequencies and pairwise linkage disequilibria of 13 variants in the EDN1 gene of 298 young males, the majority of German ancestry. Our analysis comprises all common variants in the five exons and flanking intronic regions, as well as known polymorphisms in the promoter sequence. In addition to previously analyzed polymorphisms, our haplotype reconstruction included five recently described variants and was done by using three different algorithms to allow inference of result stability. More than 30 haplotypes were predicted. All haplotypes with frequencies > or = 1% were inferred by all three methods and can be described by seven haplotype tagging single-nucleotide polymorphisms (htSNPs), reducing the genotyping load to 65%. Three of these haplotypes with frequencies of about 11%, 9%, and 4% had been mistaken for one haplotype in the previous analysis, which included only six polymorphisms, some of them not being htSNPs. Systematic analysis of sequence variability and comprehensive haplotype analysis of the EDN1 gene determined a substantial part of its genetic variability for further association studies and helped to reduce the genotyping load for common phenotypes.
    Genetic Testing 09/2006; 10(3):163-8. DOI:10.1089/gte.2006.10.163 · 1.65 Impact Factor
  • Karla Köpke
    American Journal of Medical Genetics Part B Neuropsychiatric Genetics 02/2005; 132B(1):64. DOI:10.1002/ajmg.b.30061 · 3.27 Impact Factor
  • Zeitschrift für Gastroenterologie 01/2005; 43(05). DOI:10.1055/s-2005-919892 · 1.67 Impact Factor
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    ABSTRACT: The polymorphic angiotensinogen (AGT) gene is one of the most promising candidates for blood pressure (BP) regulation and essential hypertension. To investigate whether AGT haplotype analysis adds significant information compared to single polymorphism analysis with respect to different BP phenotypes in an untreated hypertensive sample. Two hundred and twelve untreated hypertensive subjects of Caucasian origin were genotyped for the AGT polymorphisms C-532T, A-20C, C-18T, and G-6A. In single variant analyses, untreated hypertensives, carrying the AGT -532T or -6A alleles had significantly higher systolic blood pressure (SBP) and diastolic blood pressure (DBP), as well as ambulatory BP values compared to respective non-carriers. In haplotype-based analyses, combining all four AGT promoter variants, we demonstrate that AGT haplotypes containing different allele combinations at positions -532 and -6 were significantly associated with different BP values: (1) -532T and -6A with higher, (2) -532C and -6G with lower, (3) -532C and -6A with intermediate BP values. Since the result for the -532C/-20A/-18C/-6G haplotype was due to differences between non-carriers and carriers of this haplotype on both chromosomes, a recessive inheritance model for BP effects could be assumed. Our results designate the C-532T and G-6A as the best candidates for functional studies on the AGT gene. Haplotype-based analyses should greatly aid in the dissection of the genetic basis of complex traits, such as BP regulation and hypertension.
    Journal of Hypertension 08/2004; 22(7):1289-97. DOI:10.1097/01.hjh.0000125429.28861.58 · 4.22 Impact Factor
  • Karla Köpke
    Biometrical Journal 03/2004; 46:131-131. DOI:10.1002/bimj.200490037 · 1.24 Impact Factor
  • Journal of Hypertension 01/2004; 22(Suppl. 2):S76. DOI:10.1097/00004872-200406002-00260 · 4.22 Impact Factor
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    ABSTRACT: The frequency of functionally important mutations and alleles of genes coding for xenobiotic metabolizing enzymes shows a wide ethnic variation. However, little is known of the frequency distribution of the major allelic variants in the Russian population. Using polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) genotyping assays and the real-time PCR with fluorescent probes, the frequencies of functionally important variants of the cytochromes P450 (CYP) 2C9, 2C19, 2D6, 1A1 as well as arylamine N-acetyltransferase 2 (NAT2) and P-glycoprotein (MDR1) were determined in a sample of 290 Russian volunteers derived from Voronezh area. CYP2C9*2 and * 3 alleles were found with allelic frequencies of 10.5% and 6.7%, respectively. The novel intron-2 T>C mutation at exon 2 +73 bp occurred in 24.8% of alleles. CYP2C19*2 and *3 alleles occurred in 11.4% and 0.3%, respectively. Six persons (2.1%) carried two of these CYP2C19 alleles responsible for poor metabolizing activity. Of all subjects, 5.9% were CYP2D6 poor metabolizers, whereas 3.4% were addressed to ultra-rapid metabolizers (CYP2D6*1x2/*1). The CYP1A1*2A allele was found in 4.7%, *2B in 5.0%, *4 in 2.6%, and the 5'-mutations -3219C>T, -3229G>A, and the novel -4335G>A in 6.0%, 2.9% and 26.0% of alleles, respectively. Genotyping of eight different single nucleotide polymorphisms in the NAT2 gene provided in 58.0% a genotype associated with slow acetylation. The MDR1 triple variants G2677T and G2677A in exon 21 had an allelic frequency of 41.9% and 3.3%, respectively, and the variant C3435T in exon 26 one of 54.3%. Frequencies of functionally important haplotypes were calculated. The overview of allele distribution of important xenobiotic-metabolizing enzymes among a Russian population shows similarity to other Caucasians. The data will be useful for clinical pharmacokinetic investigations and for drug dosage recommendations in the Russian population.
    European Journal of Clinical Pharmacology 08/2003; 59(4):303-12. DOI:10.1007/s00228-003-0606-2 · 2.70 Impact Factor
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    ABSTRACT: The endothelin-converting enzyme (ECE)-1 gene is a candidate for human blood pressure (BP) regulation and we report the identification of the new gene variants T-839G, C-338A, L75F, A677V and C+295T. Transient transfection of the reporter constructs containing the -338A allele showed an increase in promoter activity compared with the wild-type promoter. EMSA revealed the specific binding of E2F-2 to both ECE-1b promoter sequences, with the -338A allele being associated with an increased affinity to E2F-2 compared with -338C. The clinical relevance of this finding was analyzed in 704 hypertensive patients. In untreated hypertensive women, both the -338A and -839G alleles were significantly associated with ambulatory BP values. This study provides the first evidence of a link between the cell-cycle-associated E2F family and BP regulation via a component of the endothelin system.
    Human Molecular Genetics 03/2003; 12(4):423-33. · 6.68 Impact Factor
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    Christian Meisel, Karla Köpke, Ivar Roots
    New England Journal of Medicine 02/2003; 348(5):468-70; author reply 468-70. DOI:10.1056/NEJM200301303480518 · 54.42 Impact Factor
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    ABSTRACT: We investigated the effect of polymorphisms in the P-glycoprotein (P-gp) MDR1 gene on steady-state pharmacokinetics of digoxin in Caucasians. According to earlier data, homozygous TT of the exon 26 complementary deoxyribonucleic acid (cDNA) 3435C>T polymorphism was associated with low P-gp expression in the human intestine. Eight healthy male homozygous carriers of the wild-type exon-26 3435C>T (CC), 8 heterozygous subjects (CT), and 8 homozygous mutant (TT) subjects were selected. Seven further MDR1 polymorphisms were determined. Digoxin was administered orally twice daily on the first two study days; on days 3 to 5, 0.25 mg was given in the morning. On day 5, kinetic parameters were analyzed for genotype-phenotype and haplotype-phenotype relationships. The area under the plasma concentration-time curve from time zero to 4 hours [AUC(0-4)] (P =.042) and C(max) (P =.043) values of digoxin were higher in subjects with the 3435TT genotype than in those with the 3435CC. No influence of other single nucleotide polymorphisms (SNPs) on digoxin parameters was detected. Comparison of genotypes deduced from SNPs 2677G>T (exon 21) and 3435C>T revealed significant differences for AUC(0-4) (P =.034) and C(max) (P =.039), which were substantiated by haplotype analysis. Haplotype 12 (2677G/3435T), which had a frequency of 13.3% in a randomly drawn Caucasian sample (n = 687), was associated (Mann-Whitney test) with higher AUC(0-4) values (P =.009) than were found in noncarriers (mean +/- SD, 5.7 +/- 0.9 microg. h/L [n = 7] versus 4.8 +/- 0.9 microg. h/L [n = 17]). Haplotype 11 (2677G/3435C) had lower AUC(0-4) values (P =.013) compared with those of noncarriers (mean +/- SD, 4.7 +/- 0.9 microg. h/L [n = 16] versus 5.6 +/- 0.9 microg. h/L [n = 8]). Results of haplotype analysis match data of other MDR1 studies. Haplotype 12 codes for high values of AUC(0-4) and C(max) of orally administered digoxin. Analysis of MDR1 haplotypes is superior to unphased SNP analysis to predict MDR1 phenotype.
    Clinical Pharmacology &#38 Therapeutics 11/2002; 72(5):584-94. DOI:10.1067/mcp.2002.129196 · 7.39 Impact Factor
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    ABSTRACT: Rare but striking individual differences in responsiveness to cannabinoids have been observed that might involve mutations in the gene encoding the brain-expressed cannabinoid receptor. In a preliminary study, the human CB1 cannabinoid receptor coding region was comparatively sequenced in different groups of individuals: one group showed acute psychotic symptoms after cannabis intake, while another group did not develop any psychopathology after long-term heavy cannabis abuse. No evidence for structural mutations was obtained, which might provide some insight into the molecular basis of individually different responsiveness to cannabinoids. Comparison of CB1 cannabinoid receptor amino acid sequences between species substantiated evidence that the protein sequence is relatively well conserved.
    Psychiatric Genetics 01/2001; 10(4):173-7. DOI:10.1097/00041444-200010040-00004 · 2.27 Impact Factor
  • Human Mutation 01/2001; 16(6):534. DOI:10.1002/1098-1004(200012)16:6<534::AID-HUMU24>3.0.CO;2-X · 5.05 Impact Factor

Publication Stats

824 Citations
125.21 Total Impact Points

Institutions

  • 2010–2013
    • Robert Koch Institut
      • Department for Infectious Disease Epidemiology
      Berlín, Berlin, Germany
  • 2000–2008
    • Charité Universitätsmedizin Berlin
      • Institute of Clinical Pharmacology and Toxicology
      Berlin, Land Berlin, Germany
    • Max-Delbrück-Centrum für Molekulare Medizin
      Berlín, Berlin, Germany