German Study Population Research Articles

The use of LNG-IUS-19.5 mg in daily gynecological routine practice in Germany: data from the Kyleena™ Satisfaction Study (KYSS)

PurposeThe Kyleena™ Satisfaction Study (KYSS) provided the first data on 19.5 mg levonorgestrel-releasing intrauterine system (LNG-IUS-19.5 mg) use in routine clinical practice. Here we report results from the German participants in KYSS.MethodsThis prospective, observational, single-arm cohort study recruited women who independently chose to use LNG-IUS-19.5 mg during routine counseling in Germany. Overall satisfaction and bleeding profile satisfaction, continuation rates, and safety profile were evaluated at 12 months or premature end of observation (EoO).ResultsIn the German study population, LNG-IUS-19.5 mg placement was attempted in 508 women and successful in 506 women. Mean age was 32.3 years, and 60.0% (n = 305/508) were parous. Placement was considered easy and associated with no more than mild pain, even in younger and nulliparous participants. Of those with satisfaction data available, 87.6% (n = 388/443) were satisfied with LNG-IUS-19.5 mg at 12 months/EoO. Satisfaction was similar for parous (86.9%, n = 238/274) and nulliparous (88.8%, n = 150/169) women, and was independent of age, prior contraceptive method, or reason for choosing LNG-IUS-19.5 mg. Most participants (73.6%, n = 299/406) were also satisfied with their bleeding profile at 12 months/EoO, independent of parity, age, prior contraceptive method, presence of amenorrhea or dysmenorrhea severity. The 12-month continuation rate was 84.1% (n = 427/508). Most discontinuations were due to loss to follow-up (8.5%, n = 43/508) or treatment-emergent adverse events (TEAEs) (4.7%, n = 24/508). TEAEs were reported in 12.6% (n = 64) of participants, with 9.3% (n = 47) considered to have an LNG-IUS-19.5 mg-related TEAE.ConclusionOur real-world findings on LNG-IUS-19.5 mg use in German KYSS participants reflected its suitability for a broad population, including young and nulliparous women.Clinical trial registrationNCT03182140 (date of registration: June 2017).

Radiological assessment of periodontal ligament space visibility on third molars for forensic age assessment — a comparison study of three different staging scales

Various staging scales have been proposed for the assessment of the visibility of the periodontal ligament space of mandibular third molars on dental panoramic radiographs (PANs) for forensic age assessment in living individuals. However, up to now, there has been no systematic comparison between these staging scales available. We directly compared the 2010 staging scale proposed by Olze et al. with the 2017 staging by Lucas et al. and the 2020 staging by Guo et al. in a German study population. We evaluated 233 PANs from 115 females and 118 males aged 20.0 to 40.9 years using three independent examiners, with one examiner conducting two assessments. We examined the correlation between age and stage, as well as the inter- and intra-rater reliabilities. While the point estimates for the correlation coefficient and the reliability measures were lowest for the Guo scale and highest for the Olze scale, confidence intervals showed a large overlap, particularly for the scales of Olze et al. and Lucas et al. The correlation coefficients between stage and age were consistently lower in females than in males across all methods. In summary, we showed that the staging scales of Olze et al. and Lucas et al. were very similar. The Olze method showed higher point estimates across all analyses, and because there are more reference data available for this method, we argue that it should be preferred as the method of choice for further studies in the field. However, Guo method could be considered for instances, in which the inter-radicular periodontal ligament is not evaluable.

162P MammaPrint 10-year follow up results from a German breast cancer cohort study

MammaPrint (MP) is a 70-gene signature, which has been validated in multiple studies and has proven to be a powerful predictor of risk of recurrence in patients with breast cancer (BC). In a German validation study using samples from the Patients Tumor Bank of Hope (PATH), the degree of concordance between MP and clinical risk classifications valid at that time has been determined retrospectively. MP use was shown to be feasible in a German study population revealing a change in treatment recommendation in 40% of patients (Gevensleben H et al.

The reliability and relative validity of predefined dietary patterns were higher than that of exploratory dietary patterns in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam population.

The aim of this study was to assess the ability of the FFQ to describe reliable and valid dietary pattern (DP) scores. In a total of 134 participants of the European Prospective Investigation into Cancer and Nutrition-Potsdam study aged 35-67 years, the FFQ was applied twice (baseline and after 1 year) to assess its reliability. Between November 1995 and March 1997, twelve 24-h dietary recalls (24HDR) as reference instrument were applied to assess the validity of the FFQ. Exploratory DP were derived by principal component analyses. Investigated predefined DP were the Alternative Healthy Eating Index (AHEI) and two Mediterranean diet indices. From dietary data of each FFQ, two exploratory DP were retained, but differed in highly loading food groups, resulting in moderate correlations (r 0·45-0·58). The predefined indices showed higher correlations between the FFQ (r(AHEI) 0·62, r(Mediterranean Diet Pyramid Index (MedPyr)) 0·62 and r(traditional Mediterranean Diet Score (tMDS)) 0·51). From 24HDR dietary data, one exploratory DP retained differed in composition to the first FFQ-based DP, but showed similarities to the second DP, reflected by a good correlation (r 0·70). The predefined DP correlated moderately (r 0·40-0·60). To conclude, long-term analyses on exploratory DP should be interpreted with caution, due to only moderate reliability. The validity differed extensively for the two exploratory DP. The investigated predefined DP showed a better reliability and a moderate validity, comparable to other studies. Within the two Mediterranean diet indices, the MedPyr performed better than the tMDs in this middle-aged, semi-urban German study population.

Perceived environmental barriers for people with spinal cord injury in Germany and their influence on quality of life.

The German Spinal Cord Injury Survey is part of the International Spinal Cord Injury Survey, which aims to collect data about the life experience of persons with spinal cord injury worldwide. This paper reports on the perceived environmental barriers of the German study population and their associations with quality of life. Cross-sectional explorative observational study using survey data. A total of 1,479 persons with spinal cord injury aged 18 years and older. After descriptive analyses, exploratory factor analysis was used to build groups of environmental barriers. Logistic regressions were performed to assess correlates of perceived environmental barriers. Spearman's correlations were used to analyse the association between perceived barriers and quality of life. Barriers regarding infrastructure had a relatively large impact. Barriers in relation to people's attitudes towards spinal cord injury and the equipment of people with spinal cord injury had a relatively small impact on the lives of people with spinal cord injury. Several subpopulations showed a higher risk in experiencing barriers. Quality of life decreased with increasing experience of barriers. The most life-hardening barriers were identified related to infrastructure, a category in which most barriers are modifiable, for example, buildings or transportation.

Human biomonitoring pilot study DEMOCOPHES in Germany: Contribution to a harmonized European approach.

Human biomonitoring (HBM) is an effective tool to assess human exposure to environmental pollutants, but comparable HBM data in Europe are lacking. In order to expedite harmonization of HBM studies on a European scale, the twin projects COPHES (Consortium to Perform Human Biomonitoring on a European Scale) and DEMOCOPHES (Demonstration of a study to Coordinate and Perform Human Biomonitoring on a European Scale) were formed, comprising 35 partners from 27 European countries. In COPHES a research scheme and guidelines were developed to exemplarily measure in a pilot study mercury in hair, cadmium, cotinine and several phthalate metabolites in urine of 6-11year old children and their mothers in an urban and a rural region. Seventeen European countries simultaneously conducted this cross-sectional DEMOCOPHES feasibility study. The German study population was taken in the city of Bochum and in the Higher Sauerland District, comprising 120 mother-child pairs. In the present paper features of the study implementation are presented. German exposure concentrations of the pollutants are reported and compared with European average concentrations from DEMOCOPHES and with those measured in the representative German Environmental Survey (GerES IV). German DEMOCOPHES concentrations for mercury and cotinine were lower than the European average. However, 47% of the children were still exposed to environmental tobacco smoke (ETS) outside their home, which gives further potential for enhancing protection of children from ETS. Compared with samples from the other European countries German participating children had lower concentrations of the phthalate metabolites MEP and of the sum of 3 DEHP-metabolites (MEHP, 5OH-MEHP and 5oxo-MEHP), about the same concentrations of the phthalate metabolites MBzP and MiBP and higher concentrations of the phthalate metabolite MnBP. 2.5% of the German children had concentrations of the sum of 4 DEHP-metabolites and 4.2% had concentrations of MnBP that exceeded health based guidance values, indicating reasons for concern. Continuous HBM is necessary to track changes of pollutant exposure over time. Therefore Germany will continue to cooperate on the harmonisation of European human biomonitoring to support the chemicals regulation with the best possible exposure data to protect Europe's people against environmental health risks.

The Developmental Coordination Disorder Questionnaire—German Version—in a Pediatric Outpatient Clinic for Communication Disorders

Aims: Children with speech disorder, hearing loss, or ASS often show comorbidity in motoric skills. Can parents identify and describe it with the DCDQ-G correctly? Methods: The DCDQ-G is a screening questionnaire for parents to detect developmental coordination disorders. The results of the questionnaire were compared with the neuromotoric skills made by a pediatrician or child neurologist. Parents of 119 children, aged 5.0 to 7.11 years completed the DCDQ-G. Most of the children presented speech disorders, hearing loss, or ASS. Results: We screened 119 children. Data from 92 were complete, including 22 children with migrational background (23.9%). Overall, 15 incomplete data sets were from parents with migrational background (55%). The average age was 5.10 years, including 78 boys (65.5%) and 52 girls (34.5%). The results were compared with the original data from Canada (Wilson et al 2009) and the results from the German study (Kennedy-Behr et al 2013). The specify and sensitivity in our whole group and in the study group are comparable to the results of the Canadian and German study populations. The prevalence of how parents correctly judge the motoric skills of their children is also comparable. Conclusion: The DCDQ-G is quite a useful screening instrument for parents to judge the neuromotoric development of their children in a pediatric outpatient clinic for communication disorders. The results are similar to the original study from Canada and the evaluation of the German DCDQ version in Germany. The results show some of the questions (Question 8 and 9) seem to be difficult for parents of preschool children to answer. Keywords: developmental coordination disorder.

Quality of life in partners of patients with localised prostate cancer

The diagnosis of prostate cancer and the following treatment does not only affect the patient, but also his partner. Partners often suffer even more severely from psychological distress than the patients themselves. This analysis aims to describe the quality of life (QoL) after the cancer diagnosis over time and to identify the effects of possible predictors of partners' quality of life in a German study population. Patients with localised prostate cancer and their partners were recruited from a prospective multicenter study in Germany, the Prostate Cancer, Sexuality, and Partnership (ProCaSP) Study. At five observation times during the follow-up period of 2years after diagnosis, QoL (EORTC QLQ-C30) and personal, social, and cancer-related health factors as well as adaptation and coping factors of 293 couples were observed and analysed with mixed effects analysis. The men's prostate cancer diagnosis had a small, but significant impact on their partner's QoL. However, QoL of partners was most affected by the partners' own physical health and psychological condition, time, and their relationship quality. The finding that average QoL increased again 3months after diagnosis and later should give partners faith and hope for the future. The identified most important predictors of partners' QoL are potentially susceptible to intervention, and further research on target groups in special need of support and on adequate interventions is needed.

Nutritional Status in Sick Children and Adolescents Is Not Accurately Reflected by BMI-SDS

Objective: Nutritional status provides helpful information of disease severity and treatment effectiveness. Body mass index standard deviation scores (BMI-SDS) provide an approximation of body composition and thus are frequently used to classify nutritional status of sick children and adolescents. However, the accuracy of estimating body composition in this population using BMI-SDS has not been assessed. Thus, this study aims to evaluate the accuracy of nutritional status classification in sick infants and adolescents using BMI-SDS, upon comparison to classification using percentage body fat (%BF) reference charts. Design: BMI-SDS was calculated from anthropometric measurements and %BF was measured using dual-energy x-ray absorptiometry (DXA) for 393 sick children and adolescents (5 months–18 years). Subjects were classified by nutritional status (underweight, normal weight, overweight, and obese), using 2 methods: (1) BMI-SDS, based on age- and gender-specific percentiles, and (2) %BF reference charts (standard). Linear regression and a correlation analysis were conducted to compare agreement between both methods of nutritional status classification. %BF reference value comparisons were also made between 3 independent sources based on German, Canadian, and American study populations. Results: Correlation between nutritional status classification by BMI-SDS and %BF agreed moderately (r 2 = 0.75, 0.76 in boys and girls, respectively). The misclassification of nutritional status in sick children and adolescents using BMI-SDS was 27% when using German %BF references. Similar rates observed when using Canadian and American %BF references (24% and 23%, respectively). Conclusions: Using BMI-SDS to determine nutritional status in a sick population is not considered an appropriate clinical tool for identifying individual underweight or overweight children or adolescents. However, BMI-SDS may be appropriate for longitudinal measurements or for screening purposes in large field studies. When accurate nutritional status classification of a sick patient is needed for clinical purposes, nutritional status will be assessed more accurately using methods that accurately measure %BF, such as DXA.

Genetic variants in Protocadherin‐1, bronchial hyper‐responsiveness, and asthma subphenotypes in German children

Recently, Protocadherin-1 (PCDH1) was reported as a novel susceptibility gene for bronchial hyper-responsiveness (BHR) and asthma. PCDH1 is located on chromosome 5q31-33, in the vicinity of several known candidate genes for asthma and allergy. To exclude that the associations observed for PCDH1 originate from the nearby cytokine cluster, an extensive linkage disequilibrium (LD) analysis was performed. Effects of polymorphisms in PCDH1 on asthma, BHR, and related phenotypes were studied comprehensively. Genotype information was acquired from Illumina HumanHap300Chip genotyping, MALDI-TOF MS genotyping, and imputation. LD was assessed by Haploview 4.2 software. Associations were investigated in a population of 1454 individuals (763 asthmatics) from two German study populations [MAGICS and International Study of Asthma and Allergies in Childhood phase II (ISAAC II)] using logistic regression to model additive effects. No relevant LD between PCDH1 tagging polymorphisms and 98 single nucleotide polymorphisms within the cytokine cluster was detected. While BHR was not associated with PCDH1 polymorphisms, significant associations with subphenotypes of asthma were observed. Protocadherin-1 polymorphisms may specifically affect the development of non-atopic asthma in children. Functional studies are needed to further investigate the role of PCDH1 in BHR and asthma development.

Anthocyanins in the diet of children and adolescents: intake, sources and trends

Anthocyanin intake estimations in large cohorts include almost exclusively adults. For the purpose of early dietary prevention, however, it is of great interest to estimate anthocyanin intake of children and adolescents. Anthocyanidin content values from the USDA Database (excluding the values for bananas and nuts) were assigned to foods consumed by 4-18-year-old participants of the DONALD Study. Between 1990 and 2009, 920 participants provided 6,707 3-day weighed dietary records. Intake of anthocyanins (expressed as their aglycones anthocyanidins) and their food sources were determined. For investigating age and time trends in anthocyanidin density (mg/MJ), a polynomial mixed regression model was built. We found the estimated median anthocyanidin intake to be around 6 mg/day, strawberries representing the main source. Anthocyanidin density of the diet was about 0.2 mg/MJ higher in girls than in boys, decreased with age, decreased over time in the first half of the study period and increased over time thereafter. Anthocyanin intake in the young is characterised by differences in anthocyanidin density of the diet between girls and boys and by decreasing density from young childhood to adolescence. Observations in this German study population should be extended by further studies in other countries.

Deficiency of immunity to poliovirus type 3: a lurking danger?

BackgroundEurope was certified to be polio-free in 2002 by the WHO. However, wild polioviruses remain endemic in India, Pakistan, Afghanistan, and Nigeria, occasionally causing polio outbreaks, as in Tajikistan in 2010. Therefore, effective surveillance measures and vaccination campaigns remain important. To determine the poliovirus immune status of a German study population, we retrospectively evaluated the seroprevalence of neutralizing antibodies (NA) to the poliovirus types 1, 2 and 3 (PV1, 2, 3) in serum samples collected from 1,632 patients admitted the University Hospital of Frankfurt am Main, Germany, in 2001, 2005 and 2010.MethodsTesting was done by using a standardized microneutralization assay.ResultsLevel of immunity to PV1 ranged between 84.2% (95%CI: 80.3-87.5), 90.4% (88.3-92.3) and 87.5% (85.4-88.8) in 2001, 2005 and 2010. For PV2, we found 90.8% (87.5-90.6), 91.3% (89.3-93.1) and 89.8% (88.7-90.9), in the same period. Seroprevalence to PV3 was 76.6% (72.2-80.6), 69.8% (66.6-72.8) and 72.9% (67.8-77.5) in 2001 and 2005 and 2010, respectively. In 2005 and 2010 significant lower levels of immunity to PV3 in comparison to PV1 and 2 were observed. Since 2001, immunity to PV3 is gradually, but not significantly decreasing.ConclusionImmunity to PV3 is insufficient in our cohort. Due to increasing globalization and worldwide tourism, the danger of polio-outbreaks is not averted - even not in developed countries, such as Germany. Therefore, vaccination remains necessary.

Alcohol and drug dependence in adults with attention-deficit/hyperactivity disorder: Data from Germany

Background and Objectives: The objective of the present study was to obtain information about the prevalence of addiction disorders in ADHD patients in a German study population, to compare the prevalence of addiction disorders in ADHD patients to that in the normal population according to the German Epidemiological Addiction Survey, and to determine which drugs are consumed most by ADHD patients. Participants: The sample consisted of 61 patients (average age 35.11 ± 9.33 years) from our ADHD consultation who were consecutively included in our study over a period of 12 months. Measurements: We diagnosed ADHD according to DSM-IV-R and by assessing the WURS-k, CAARS and BROWN ADD scales. For diagnosing addiction we conducted the EuropASI, the IDCL, the QOD and the FTNA. For differential diagnosis we assessed the SCL-K. Results: About half of our study population of ADHD patients were diagnosed with a dependence disorder (50.8%, n = 31). Twenty one dot three percent (n = 13) were suffering from an alcohol dependence, 13.1% (n = 8) from a substance use disorder (SUD) and 18% (n = 11) from a combination of both addictions. The drug consumed most commonly by ADHD paALCOHOL AND DRUG DEPENDENCE IN ADULTS WITH ATTENTION-DEFICIT... 151

Long‐term outcome after intrauterine laser treatment for twin–twin transfusion syndrome

Twin-twin transfusion syndrome (TTTS) is a severe complication occurring in about 10% of monochorionic twin pregnancies. The chronic unbalanced transfusion of blood across placental vascular communications from the donor to the recipient twin may lead to impairment of various organ systems in the affected twins. In Hamburg, Germany, since 1995 patients with TTTS were treated with fetoscopic laser coagulation as the first causal therapeutic strategy. All survivors after laser surgery were followed up in the University Children's Hospital in Bonn, Germany. In this article, we summarize long-term follow-up studies from our German study population and compare our results with data from the literature.

Comparison of MammaPrint and TargetPrint results with clinical parameters in German patients with early stage breast cancer

The 70-gene expression profile MammaPrint is a powerful prognostic indicator for disease outcome in breast cancer patients with improved prediction of recurrence risk compared to currently used guidelines. The microarray-based test TargetPrint further provides reliable, quantitative assessment of mRNA expression levels of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). This study was performed as a validation of MammaPrint and TargetPrint in an unselected German breast cancer population and was designed to determine the degree of concordance with currently applied clinical parameters. One hundred and forty cases of breast cancer stage I and II were classified as being low or high risk for distant metastasis using MammaPrint. Results were compared to current clinical risk classifications and adjuvant treatment management. Immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH)/chromogenic in situ hybridization (CISH) assessments of ER, PR and HER2 were further compared with gene expression read-outs using TargetPrint. Thirty-two percent of patients (19/59) with a poor prognosis-signature identified via MammaPrint did not receive adjuvant systemic treatment apart from endocrine therapy and were potentially undertreated; whereas 42% (35/77) of patients with a good prognosis-signature received chemotherapy and were potentially overtreated. Comparison of microarray receptor results with IHC and FISH/CISH were concordant in 97% for ER; 86% for PR; and 94% for HER2. In this German study population, MammaPrint would have resulted in altered treatment advice for adjuvant systemic therapy in 40% of patients. Furthermore, TargetPrint presented high concordance for ER, PR and Her2 with IHC and FISH/CISH analysis.

PC-FACS

PC-FACS

Rare TLR2 mutations reduce TLR2 receptor function and can increase atopy risk

Common genetic variations in toll-like receptor 2 (TLR2), an innate pathogen recognition receptor, may influence the development of atopic diseases. So far, very little is known about the role of rare TLR2 mutations in these diseases. We investigated the functional properties of six rare amino acid changes in TLR2 (and one amino acid change in a TLR2 pseudogene) and studied their effect on atopic sensitization and disease. We identified rare TLR2 mutations leading to amino acid changes from databases. Functional effects of TLR2 variants were analyzed by NF-kappaB-dependent luciferase reporter assay and interleukin-8 enzyme linked immunosorbent assay in vitro. The frequency of these mutations was determined in a random sample of the general population (n = 368). Association with atopic diseases were studied in a cross sectional German study population (n = 3099). Three out of six mutations in the TLR2 gene altered receptor activity in vitro. Out of these, only the minor allele of R753Q occurred reasonably frequent in the German population (minor allele frequency 3%). The risk to develop atopy increased by 50% in carriers of the 753Q allele (P = 0.021) and total (P = 0.040) as well as allergen specific serum IgE levels (P = 0.011) were significantly elevated. The rare but functionally relevant mutation R753Q in TLR2 may significantly affect common conditions such as atopic sensitization in the general population.

Negative association of the chemokine receptor CCR5 d32 polymorphism with systemic inflammatory response, extra-articular symptoms and joint erosion in rheumatoid arthritis

IntroductionChemokines and their receptors control immune cell migration during infections as well as in autoimmune responses. A 32 bp deletion in the gene of the chemokine receptor CCR5 confers protection against HIV infection, but has also been reported to decrease susceptibility to rheumatoid arthritis (RA). The influence of this deletion variant on the clinical course of this autoimmune disease was investigated.MethodsGenotyping for CCR5d32 was performed by PCR and subsequent electrophoretic fragment length determination. For the clinical analysis, the following extra-articular manifestations of RA were documented by the rheumatologist following the patient: presence of rheumatoid nodules, major organ vasculitis, pulmonary fibrosis, serositis or a Raynaud's syndrome. All documented CRP levels were analyzed retrospectively, and the last available hand and feet radiographs were analyzed with regards to the presence or absence of erosive disease.ResultsAnalysis of the CCR5 polymorphism in 503 RA patients and in 459 age-matched healthy controls revealed a significantly decreased disease susceptibility for carriers of the CCR5d32 deletion (Odds ratio 0.67, P = 0.0437). Within the RA patient cohort, CCR5d32 was significantly less frequent in patients with extra-articular manifestations compared with those with limited, articular disease (13.2% versus 22.8%, P = 0.0374). In addition, the deletion was associated with significantly lower average CRP levels over time (median 8.85 vs. median 14.1, P = 0.0041) and had a protective effect against the development of erosive disease (OR = 0.40, P = 0.0047). Intriguingly, homozygosity for the RA associated DNASE2 -1066 G allele had an additive effect on the disease susceptibility conferred by the wt allele of CCR5 (OR = 2.24, P = 0.0051 for carrier of both RA associated alleles)ConclusionsThe presence of CCR5d32 significantly influenced disease susceptibility to and clinical course of RA in a German study population. The protective effect of this deletion, which has been described to lead to a decreased receptor expression in heterozygous patients, underlines the importance of chemokines in the pathogenesis of RA.

Domestic cat allergen and allergic sensitisation in young children

Studies have presented conflicting associations between cat allergen exposure and sensitisation and atopic disease. We therefore investigated the association between the observed domestic cat allergen level and cat sensitisation in young children in four study populations from three European countries. We recruited children from a nested case-control study, which is composed of four ongoing birth cohorts conducted in three European countries. Children at 2-4 years of age in the four cohorts who were sensitised to cat allergens (n=106) were compared with 554 non-sensitised children (controls). House dust samples were collected when the children were 5 to 7 years old, and cat allergen levels were measured in ng/g dust and ng/m(2) surface area. In the German study population we found a positive association between domestic cat allergen in house dust and cat sensitisation (OR (CI)=3.01 (1.16, 7.99)) while in the Swedish study population, we found a negative association (OR (CI)=0.41 (0.16, 0.98)). No association was found in the Dutch study population (OR (CI)=0.83 (0.22, 2.93)). Looking into the family history of cat keeping, we found the lowest prevalence of cat sensitisation in children who were cat owners at the age of blood sampling (11%) and the highest prevalence was found in those who have had a cat but not anymore, at the age of blood sampling (41%). The mixed results may be explained by differences in age and avoidance patterns.

Association of Prostaglandin E Synthase 2 (PTGES2) Arg298His Polymorphism with Type 2 Diabetes in Two German Study Populations

On the basis of its chromosomal localization and its role in the synthesis of the antilipolytic compound prostaglandin E(2), the prostaglandin E synthase 2 (PTGES2) is a candidate gene for type 2 diabetes. The aim of the present study was to investigate whether genetic variants in the PTGES2 gene are associated with type 2 diabetes. Sequencing of the PTGES2 gene revealed one nonsynonymous coding single-nucleotide polymorphism (SNP) (Arg298His, rs13283456) and a previously unknown promoter SNP g.-417G>T. Both SNPs and additional haplotype tagging SNPs (rs884115, rs10987883, rs4837240) were genotyped in a nested case-control study of 192 incident type 2 diabetes subjects and 384 controls (European Prospective Investigation into Cancer and Nutrition-Potsdam). Carriers of the minor allele of Arg298His had a lower risk to develop the disease [odds ratio (OR) 0.63, 95% confidence interval (CI) 0.41-0.97, P = 0.04], compared with homozygous individuals with the common allele. The PTGES2 Arg298His polymorphism was reinvestigated in a population-based cross-sectional study (Cooperative Health Research in the Augsburg Region) consisting of 239 individuals with impaired glucose tolerance, 226 with type 2 diabetes, and 863 normoglycemic controls. In this study population, the Arg298His polymorphism was significantly associated with impaired glucose tolerance (OR 0.68, 95% CI 0.50-0.93, P = 0.007) and type 2 diabetes (OR 0.61, 95% CI 0.43-0.86, P = 0.004). A pooled analysis of data from both study populations revealed reduced risk of type 2 diabetes (OR 0.62, 95% CI 0.47-0.81, P = 0.0005) in PTGES2 298His allele carriers. We obtained evidence from two Caucasian study populations that the His298-allele of PTGES2 Arg298His confers to reduced risk of type 2 diabetes.