Christian Schwahn

Cohort Profile: The Study of Health in Pomerania

Henry Volzke, y Dietrich Alte,1y Carsten Oliver Schmidt, Dorte Radke, Roberto Lorbeer, Nele Friedrich, Nicole Aumann, Katharina Lau, Michael Piontek, Gabriele Born, Christoph Havemann, Till Ittermann, Sabine Schipf, Robin Haring, Sebastian E Baumeister, Henri Wallaschofski, Matthias Nauck, Stephanie Frick, Andreas Arnold, Michael Junger, Julia Mayerle, Matthias Kraft, Markus M Lerch, Marcus Dorr, Thorsten Reffelmann, Klaus Empen, Stephan B Felix, Anne Obst, Beate Koch, Sven Glaser, Ralf Ewert, Ingo Fietze, Thomas Penzel, Martina Doren, Wolfgang Rathmann, Johannes Haerting, Mario Hannemann, Jurgen Ropcke, Ulf Schminke, Clemens Jurgens, Frank Tost, Rainer Rettig, Jan A Kors, Saskia Ungerer, Katrin Hegenscheid, Jens-Peter Kuhn, Julia Kuhn, Norbert Hosten, Ralf Puls, Jorg Henke, Oliver Gloger, Alexander Teumer, Georg Homuth, Uwe Volker, Christian Schwahn, Birte Holtfreter, Ines Polzer, Thomas Kohlmann, Hans J Grabe, Dieter Rosskopf, Heyo K Kroemer, Thomas Kocher, Reiner Biffar,17,y Ulrich John20y and Wolfgang Hoffmann1y

The prevalence of undiagnosed thyroid disorders in a previously iodine-deficient area.

OBJECTIVE The aim of the present study was to analyze the current status of morphologic and functional thyroid abnormalities in a previously iodine-deficient area. METHODS The population based Study of Health in Pomerania (SHIP) comprised 4310 participants, aged 20-79 years. Thyroid function (thyrotropin [TSH] free triiodothyronine [FT(3)], and free thyroxine [FT(4)]) and serum autoantibodies to thyroperoxidase (TPOAb) were evaluated from blood samples. Thyroid structure and size were measured by ultrasound. Data from 3941 participants with no known thyroid disorders were analyzed. RESULTS The median iodine urine excretion was 12.4 microg/dL. The rate of decreased serum TSH levels (<0.3 mIU/L) was 11.3%; 2.2% of participants had suppressed serum TSH levels (<0.1 mIU/L). The prevalence of subclinical hyperthyroidism was 1.8%, the prevalence of overt hyperthyroidism 0.4%. Elevated TSH levels were found in 1.2% of individuals. Subclinical hypothyroidism was observed in 0.5%, overt hypothyroidism in 0.7% of the sample. Elevated TPOAb were detected in 7% of subjects, 4.1% of participants had TPOAb greater than 200 IU/mL. The prevalence of goiter was 35.9%. An inhomogeneous echo pattern was detected in 35.2% and nodules in 20.2% of participants. Diffuse autoimmune thyroiditis was diagnosed in 47 subjects (1.2%). CONCLUSION There are a number of thyroid disorders in this previously iodine-deficient region. Further studies are required to investigate the change of thyroid disorders during iodine supplementation programs.

Moderation of Adult Depression by a Polymorphism in the FKBP5 Gene and Childhood Physical Abuse in the General Population

Childhood maltreatment and depressive disorders have both been associated with a dysregulation of the hypothalamic–pituitary–adrenal axis. The FKBP5 gene codes for a co-chaperone regulating the glucocorticoid-receptor sensitivity. Previous evidence suggests that subjects carrying the TT genotype of the FKBP5 gene single-nucleotide polymorphism (SNP) rs1360780 have an increased susceptibility to adverse effects of experimental stress. We therefore tested the hypothesis of an interaction of childhood abuse with rs1360780 in predicting adult depression. In all, 2157 Caucasian subjects from the Study of Health in Pomerania (German general population) completed the Beck Depression Inventory (BDI-II) and Childhood Trauma Questionnaire. The DSM-IV diagnosis of major depressive disorder (MDD) was assessed by interview. Genotypes of rs1360780 were taken from the Affymetrix Human SNP Array 6.0. Significant interaction (p=0.006) of physical abuse with the TT genotype of rs1360780 was found increasing the BDI-II score to 17.4 (95% confidence interval (CI)=12.0–22.9) compared with 10.0 (8.2–11.7) in exposed CC/CT carriers. Likewise, the adjusted odds ratio for MDD in exposed TT carriers was 8.2 (95% CI=1.9–35.0) compared with 1.3 (0.8–2.3) in exposed subjects with CC/CT genotypes. Relative excess risk due to interaction (RERI) analyses confirmed a significant additive interaction effect (RERI=6.8; 95% CI=0.64–33.7; p<0.05). In explorative analyses, the most severe degree of sexual and emotional abuse also yielded significant interaction effects (p<0.05). This study revealed interactions between physical abuse and rs1360780 of the FKBP5 gene, confirming its role in the individual susceptibility to depression. Given the large effect sizes, rs1360780 could be included into prediction models for depression in individuals exposed to childhood abuse.

Independent risk factors for gallstone formation in a region with high cholelithiasis prevalence.

Background/Aims:Cholelithiasis is a common disorder in north-eastern Germany. Analyses of risk factors for gallstone formation in this population may have high explanatory power. Gender-specific risk factors for gallstone formation and their interactions were investigated by using data of the population-based Study of Health in Pomerania (SHIP). Methods:Data of 4,202 persons aged 20–79 years were available. Cholelithiasis was defined by either a prior history of cholecystectomy or the presence of gallstones on abdominal ultrasound. Multivariable analyses were performed to identify independent risk factors for gallstone formation. Results:There were 468 persons (11.1%) with previous cholecystectomy and 423 persons (10.1%) with sonographic evidence of gallstones. Women had a twofold higher risk for cholelithiasis compared to men. Age, body mass index and low serum HDL cholesterol levels were independently associated with cholelithiasis in both men and women. In the male population, low alcohol and high coffee consumption and in the female population, low physical activity, were further independently related to gallstone formation. Additionally, sex-specific interactions between risk factors were found. Conclusions: Female sex, age and being overweight are major risk factors for gallstone formation in this region where cholelithiasis is a frequent disorder. Additional factors and interactions contribute to a gender-specific gallstone risk.

Gender Differences in the Relationship Between Periodontal Disease, Tooth Loss, and Atherosclerosis

Background and Purpose— Males carry a disproportionate burden of cardiovascular disease. Because males also bear a higher burden of periodontal disease, we investigated the existence of gender differences in the postulated relationship between periodontal infections, tooth loss, and subclinical atherosclerosis. Methods— A total of 1710 randomly enrolled participants between the ages of 45 and 75 with no history of myocardial infarction or stroke received a clinical periodontal examination, carotid scan using high-resolution B-mode ultrasound, and extensive measurements for conventional cardiovascular risk factors (age, education, smoking, alcohol, body mass index, diabetes, systolic blood pressure, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, and triglycerides) as well as markers of healthy lifestyle and social network. Results— In both genders, measures of current and long-term periodontitis worsened as tooth loss increased. In males but not females, an ≈10% difference in carotid artery plaque prevalence was observed between the lowest and highest tertiles of tooth loss (P <0.05) and long-term periodontitis (P =0.05) after multivariate adjustment. Similar patterns were observed for intima–media thickness. The influence of gender on carotid artery plaque prevalence was most evident among the younger age group (<59 years). Between genders, carotid plaque prevalence differed by 10%, 15%, and 25% across increasing levels of tooth loss, and by 5%, 15%, and 25% across increasing levels of long-term periodontitis. Conclusions— Our data suggest that tooth loss and long-term periodontitis are related to subclinical atherosclerosis in men but not women. Gender variations in cardiovascular morbidity or mortality may be explained partly by the differential contributions of novel risk factors across genders.

Serotonin transporter gene (SLC6A4) promoter polymorphisms and the susceptibility to posttraumatic stress disorder in the general population.

OBJECTIVE There has been debate whether polymorphisms within the serotonin transporter-linked polymorphic region (5-HTTLPR) moderate susceptibility to posttraumatic stress disorder (PTSD). The authors investigated 5-HTTLPR genotypes and their interaction with the number of traumatic events in the prediction of PTSD in a general population sample. METHOD Analyses were based on data from 3,045 subjects who participated in the Study of Health in Pomerania. All participants were assessed with the PTSD module of the Structured Clinical Interview for DSM-IV. The short (S)/long (L) polymorphism of 5-HTTLPR (rs4795541) and the A-G polymorphism (rs25531) were genotyped. RESULTS Among the participants, 1,663 had been exposed to at least one traumatic event, and 67 (4.0%) developed PTSD. Among those who had experienced less than three traumatic events, the lifetime prevalence of PTSD was 2.6%, 3.5%, and 4.3% for those with zero, one, and two L(A) alleles, respectively, but the lifetime prevalence was 0%, 7.3%, and 19.6%, respectively, among those with three or more traumatic experiences. This finding suggests that there is an additive excess risk for frequent trauma in the L(A)/L(A) genotype, which was confirmed by the relative excess risk due to interaction (RERI). In allelic analysis, RERI was 3.3. Thus, the odds ratio for PTSD in L(A) allele carriers exposed to three or more traumas was 3.3 times higher as a result of the interaction between PTSD and the L(A) allele. CONCLUSIONS An additive gene-environment interaction with the high expression L(A) allele of 5-HTTLPR and frequent trauma in PTSD was found. The attributable proportion indicated that more than 60% of all L(A) allele carriers who were exposed to three or more traumas developed PTSD as a result of an interaction between genotype and exposure.

Menopausal status and hepatic steatosis in a general female population

Population-based studies showed that non-alcoholic hepatic steatosis is less common in women than in men. Anti-oestrogens double the risk of non-alcoholic steatohepatitis,1 which may be interpreted as indirect evidence for a protective role of endogenous oestrogens against steatohepatitis. Experimental evidence further suggests that oestradiol causes a reduction of hepatic steatosis in mice unable to produce oestrogens.2 We thus hypothesised that the menopause as a natural state of oestrogen deficiency might increase the risk of hepatic steatosis. The Study of Health in Pomerania is a cross-sectional population-based survey in northeast Germany.3 We restricted our analyses to 808 women aged 40–59 years without seropositivity to hepatitis B antigen and anti-hepatitis C virus. The study was approved by the ethics committee of the University of Greifswald. All participants gave written informed consent. Menopause was defined as 12 consecutive months of amenorrhoea or cessation of menstruation after iatrogenic intervention. Serum glutamate oxaloacetate …

Association between type 1 and type 2 diabetes with periodontal disease and tooth loss

AIM The aim of this study was to determine whether both type 1 (T1DM) and type 2 diabetes mellitus (T2DM) are associated with increased prevalence and extent of periodontal disease and tooth loss compared with non-diabetic subjects within a homogeneous adult study population. MATERIAL AND METHODS T1DM, T2DM and non-diabetic subjects were recruited from the population-based Study of Health in Pomerania. Additionally, T1DM subjects were retrieved from a Diabetes Centre. The total study population comprised 145 T1DM and 2647 non-diabetic subjects aged 20-59 years, and 182 T2DM and 1314 non-diabetic subjects aged 50-81 years. Periodontal disease was assessed by attachment loss (AL) and the number of missing teeth. RESULTS Multivariable regression revealed an association between T1DM (p<0.001) and T2DM (p<0.01) with mean AL after full adjustment. After age stratification (p=0.04 for interaction), the effect of T2DM was only statistically significant in the 60-69-year-old subjects (B=0.90 (95% confidence intervals [95% CI]; 0.49, 1.31). T1DM was positively associated with tooth loss (adjusted, p<0.001). The association between T2DM and tooth loss was statistically significant only for females (odds ratios=1.60 [95% CI: 1.10, 2.33]). CONCLUSIONS Our study confirmed an association between both T1DM and T2DM with periodontitis and tooth loss. Therefore, oral health education should be promoted in diabetic subjects.

Epidemiology of periodontal diseases in the study of health in Pomerania

AIM The aim of this study was to assess the prevalence and extent of periodontal diseases among adults in a province in Eastern Germany. MATERIAL AND METHODS The Study of Health in Pomerania is a population-based study conducted during 1997-2001. The net random sample comprised 4310 20-81-year-old subjects. Periodontal status was assessed at four surfaces using a half-mouth recording protocol. RESULTS The prevalence of attachment loss >or=3 mm was 89.7%, with 62.8% of teeth being affected. Probing depths >or=4 mm were prevalent in 69.7% of subjects, and 29.6% of teeth were affected. 25.3% of all subjects had severe pockets (>or=6 mm). Periodontitis was significantly more prevalent in males. For attachment loss, the prevalence and extent increased significantly with increasing age, whereas probing depth values levelled off after the age of 40. In older subjects, increased recession and attachment loss were found, while the probing depth remained constant. According to the recent CDC classification, 17.6% and 33.3% of persons had severe and moderate periodontitis, respectively. The prevalence of periodontitis increased significantly with age and remained constant after the age of 50-59. CONCLUSIONS Periodontitis is more prevalent in Pomerania than in the United States or Western Europe. In older subjects, attachment loss steadily increased, while the probing depth remained constant.

Childhood maltreatment, the corticotropin-releasing hormone receptor gene and adult depression in the general population†‡

Dysregulations of the hypothalamic‐pituitary‐adrenal (HPA) axis have been implicated in the pathogenesis of depressive disorders and the corticotropin‐releasing hormone (CRH) was found to modulate emotional memory consolidation. Recently, two studies have reported an interaction between childhood abuse and the TAT–haplotype of the CRH‐Receptor Gene (CRHR1) connecting childhood adversities and genetic susceptibility to adult depression. We tested the hypothesis of an interaction of childhood maltreatment with single nucleotide polymorphisms (SNPs) and haplotypes of the CRHR1 gene not previously investigated. Caucasian subjects (n = 1,638) from the German general population (Study of Health in Pomerania, SHIP) were analyzed. As in the previous studies, childhood abuse and neglect were assessed with the Childhood Trauma Questionnaire (CTQ) and depression with the Beck Depression Inventory (BDI‐2). The CRHR1‐SNPs were genotyped on the Affymetrix Genome‐Wide Human SNP Array 6.0 platform. We identified an interaction between the TAT–haplotype and childhood physical neglect. The interaction with physical neglect showed significant (P < 0.05) results in 23 of the 28 SNPs, with rs17689882 (P = 0.0013) reaching “gene‐wide” significance. Although we did not replicate the specific interaction of abuse and the TAT–haplotype of the CRHR1 gene we confirmed the relevance of an interplay between variants within the CRHR1 gene and childhood adversities in the modulation of depression in adults. The largest effect was found for rs17689882, a SNP previously not analyzed. Relevant sample differences between this and prior studies like lower BDI‐2 scores, less childhood maltreatment and higher psychosocial functioning may account for the differences in gene–environment interaction findings.