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Background: Depression and obesity are widespread and closely linked. Brain-derived neurotrophic factor (BDNF) and vitamin D are both assumed to be associated with depression and obesity. Little is known about the interplay between vitamin D and BDNF. We explored the putative associations and interactions between serum BDNF and vitamin D levels with depressive symptoms and abdominal obesity in a large population-based cohort. Methods: Data were obtained from the population-based Study of Health in Pomerania (SHIP)-Trend (n = 3,926). The associations of serum BDNF and vitamin D levels with depressive symptoms (measured using the Patient Health Questionnaire) were assessed with binary and multinomial logistic regression models. The associations of serum BDNF and vitamin D levels with obesity (measured by the waist-to-hip ratio [WHR]) were assessed with binary logistic and linear regression models with restricted cubic splines. Results: Logistic regression models revealed inverse associations of vitamin D with depression (OR = 0.966; 95% CI 0.951–0.981) and obesity (OR = 0.976; 95% CI 0.967–0.985). No linear association of serum BDNF with depression or obesity was found. However, linear regression models revealed a U-shaped association of BDNF with WHR (p < 0.001). Conclusion: Vitamin D was inversely associated with depression and obesity. BDNF was associated with abdominal obesity, but not with depression. At the population level, our results support the relevant roles of vitamin D and BDNF in mental and physical health-related outcomes.
Background: Depression and obesity are widespread and closely linked. Brain-derived neurotrophic factor (BDNF) and vitamin D are both assumed to be associated with depression and obesity. Little is known about the interplay between vitamin D and BDNF. We explored the putative associations and interactions between serum BDNF and vitamin D levels with depressive symptoms and abdominal obesity in a large population-based cohort. Methods: Data were obtained from the population-based Study of Health in Pomerania (SHIP)-Trend (n = 3,926). The associations of serum BDNF and vitamin D levels with depressive symptoms (measured using the Patient Health Questionnaire) were assessed with binary and multinomial logistic regression models. The associations of serum BDNF and vitamin D levels with obesity (measured by the waist-to-hip ratio [WHR]) were assessed with binary logistic and linear regression models with restricted cubic splines. Results: Logistic regression models revealed inverse associations of vitamin D with depression (OR = 0.966; 95% CI 0.951–0.981) and obesity (OR = 0.976; 95% CI 0.967–0.985). No linear association of serum BDNF with depression or obesity was found. However, linear regression models revealed a U-shaped association of BDNF with WHR (p < 0.001). Conclusion: Vitamin D was inversely associated with depression and obesity. BDNF was associated with abdominal obesity, but not with depression. At the population level, our results support the relevant roles of vitamin D and BDNF in mental and physical health-related outcomes.
The Membrane Transporter OAT7 (SLC22A9) Is Not a Susceptibility Factor for Osteoporosis in Europeans
(2020)
Bone production, maintenance, and modeling are a well-balanced process involving mineralization by osteoblasts and resorption by osteoclasts. Sex steroid hormones, including their conjugated forms, contribute majorly to maintaining this balance. Recently, variants in the SLC22A9 gene have been associated with osteoporosis in Korean females. We had recently shown that SLC22A9, encoding organic anion transporter 7 (OAT7), is an uptake transporter of estrone sulfate and identified several genetic variants in Europeans leading to functional consequences in vitro. We therefore hypothesized that SLC22A9 genetic variants may contribute to the pathophysiology of osteoporosis in Europeans. To test this hypothesis, we examined the associations of SLC22A9 variants with bone quality, fractures, and bone turnover markers. We genotyped SLC22A9 variants in 5,701 (2,930 female) subjects (age range, 20–93 years) extracted from the population-based Study of Health in Pomerania (SHIP and SHIP-TREND) covered by the Illumina Infinium HumanExome BeadChip version v1.0 (Exome Chip). Descriptive data (e.g., history of fractures), ultrasonography of the calcaneus, as well as serum concentrations of carboxy-terminal telopeptide of type I collagen, amino-terminal propeptide of type I procollagen, and vitamin D were determined. Comprehensive statistical analyses revealed no association between low-frequency and rare SLC22A9 variants and bone quality, fractures, and bone turnover markers. Our results indicate that single genetic SLC22A9 variants do not have a major impact on osteoporosis risk prediction in Europeans, yet findings need to be replicated in larger-scale studies.
Abstract
Background
Twenty five‐hydroxy vitamin D (25OHD) levels have been proposed to protect against periodontitis based on in vitro and observational studies but evidence from long‐term randomized controlled trials (RCTs) is lacking. This study tested whether genetically proxied 25OHD is associated with periodontitis using Mendelian randomization (MR).
Methods
Genetic variants strongly associated with 25OHD in a genome‐wide association study (GWAS) of 417,580 participants of European ancestry were used as instrumental variables, and linked to GWAS summary data of 17,353 periodontitis cases and 28,210 controls. In addition to the main analysis using an inverse variance weighted (IVW) model, we applied additional robust methods to control for pleiotropy. We also undertook sensitivity analyses excluding single nucleotide polymorphisms (SNPs) used as instruments with potential pleiotropic effects and used a second 25OHD GWAS for replication. We identified 288 SNPs to be genome‐wide significant for 25OHD, explaining 7.0% of the variance of 25OHD levels and providing ≥90% power to detect an odds ratio (OR) of ≤ 0.97.
Results
MR analysis suggested that a 1 standard deviation increase in natural log‐transformed 25OHD was not associated with periodontitis risk (IVW OR = 1.04; 95% confidence interval (CI): 0.97–1.12; P‐value = 0.297). The robust models, replication, and sensitivity analyses were coherent with the primary analysis.
Conclusions
Collectively, our findings suggest that 25OHD levels are unlikely to have a substantial effect on the risk of periodontitis, but large long‐term RCTs are needed to derive definitive evidence on the causal role of 25OHD in periodontitis.
The Study of Health in Pomerania (SHIP), a population-based study from a rural state in northeastern Germany with a relatively poor life expectancy, supplemented its comprehensive examination program in 2008 with whole-body MR imaging at 1.5 T (SHIP-MR). We reviewed more than 100 publications that used the SHIP-MR data and analyzed which sequences already produced fruitful scientific outputs and which manuscripts have been referenced frequently. Upon reviewing the publications about imaging sequences, those that used T1-weighted structured imaging of the brain and a gradient-echo sequence for R2* mapping obtained the highest scientific output; regarding specific body parts examined, most scientific publications focused on MR sequences involving the brain and the (upper) abdomen. We conclude that population-based MR imaging in cohort studies should define more precise goals when allocating imaging time. In addition, quality control measures might include recording the number and impact of published work, preferably on a bi-annual basis and starting 2 years after initiation of the study. Structured teaching courses may enhance the desired output in areas that appear underrepresented.
The renal renin-angiotensin system (RAS) is involved in the development of chronic kidney disease. Here, we investigated whether mice with reduced renal angiotensin I-converting enzyme (ACE−/−) are protected against aristolochic acid nephropathy (AAN). To further elucidate potential molecular mechanisms, we assessed the renal abundances of several major RAS components. AAN was induced using aristolochic acid I (AAI). Glomerular filtration rate (GFR) was determined using inulin clearance and renal protein abundances of renin, angiotensinogen, angiotensin I-converting enzyme (ACE) 2, and Mas receptor (Mas) were determined in ACE−/− and C57BL/6J control mice by Western blot analyses. Renal ACE activity was determined using a colorimetric assay and renal angiotensin (Ang) (1–7) concentration was determined by ELISA. GFR was similar in vehicle-treated mice of both strains. AAI decreased GFR in controls but not in ACE−/− mice. Furthermore, AAI decreased renal ACE activity in controls but not in ACE−/− mice. Vehicle-treated ACE−/− mice had significantly higher renal ACE2 and Mas protein abundances than controls. AAI decreased renal ACE2 protein abundance in both strains. Furthermore, AAI increased renal Mas protein abundance, although the latter effect did not reach statistical significance in the ACE−/− mice. Renal Ang(1–7) concentration was similar in vehicle-treated mice of both strains. AAI increased renal Ang(1–7) concentration in the ACE−/− mice but not in the controls. Mice with reduced renal ACE are protected against AAN. Our data suggest that in the face of renal ACE deficiency, AAI may activate the ACE2/Ang(1–7)/Mas axis, which in turn may deploy its reno-protective effects.
Abstract
Aim
To examine the associations between bone turnover markers and periodontitis in two cross‐sectional population‐based studies.
Materials and Methods
We used data from two independent adult samples (N = 4993), collected within the Study of Health in Pomerania project, to analyse cross‐sectional associations of N‐procollagen type 1 amino‐terminal propeptide (P1NP), C‐terminal cross‐linking telopeptide, osteocalcin, bone‐specific alkaline phosphatase (BAP), fibroblast growth factor 23, wingless‐type mouse mammary tumour virus integration site family member 5a (WNT5A), and sclerostin values with periodontitis. Confounder‐adjusted gamma and fractional response regression models were applied.
Results
Positive associations were found for P1NP with mean pocket probing depth (PPD; eβ=1.008; 95% confidence interval [CI]: 1.001–1.015), mean clinical attachment loss (mean CAL; eβ=1.027; 95% CI: 1.011–1.044), and proportion of sites with bleeding on probing (%BOP; eβ=1.055; 95% CI: 1.005–1.109). Similar associations were seen for BAP with %BOP (eβ=1.121; 95% CI: 1.042–1.205), proportion of sites with PPD ≥4 mm (%PPD4) (eβ=1.080; 95% CI: 1.005–1.161), and sclerostin with %BOP (eβ=1.308; 95% CI: 1.005–1.704). WNT5A was inversely associated with mean PPD (eβ=0.956; 95% CI: 0.920–0.993) and %PPD4 (eβ=0.794; 95% CI: 0.642–0.982).
Conclusions
This study revealed scattered associations of P1NP, BAP, WNT5A, and sclerostin with periodontitis, but the results are contradictory in the overall context. Associations reported in previous studies could not be confirmed.
The hypothalamus–pituitary–adrenal axis is the main physiological stress response system and regulating the release of cortisol. The two corticoid receptors encoded by the genes NR3C1 and NR3C2 are the main players in regulating the physiological response to cortisol. This biological system has been linked to neurocognitive processes and memory, yet the mechanisms remain largely unclear. In two independent general population studies (SHIP, total sample size > 5500), we aim to diseantangle the effects of genetic variation, gene expression and cortisol on verbal memory and memory associated brain volume. Especially for NR3C1 results exhibited a consistent pattern of direct an interactive effects. All three biological layers, genetic variation (rs56149945), gene expression for NR3C1 and cortisol levels, were directly associated with verbal memory. Interactions between these components showed significant effects on verbal memory as well as hippocampal volume. For NR3C2 such a complex association pattern could not be observed. Our analyses revealed that different components of the stress response system are acting together on different aspects of cognition. Complex phenotypes, such as cognition and memory function are regulated by a complex interplay between different genetic and epigenetic features. We promote the glucocorticoid receptor NR3C1 as a main target to focus in the context of verbal memory and provided a mechanistic concept of the interaction between various biological layers spanning NR3C1 function and its effects on memory. Especially the NR3C1 transcript seemed to be a key element in this complex system.