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Genetic risk-factors for anxiety in healthy individuals: polymorphisms in genes important for the HPA axis.
Lindholm, H, Morrison, I, Krettek, A, Malm, D, Novembre, G, Handlin, L
BMC medical genetics. 2020;21(1):184
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Anxiety is a complex disorder that involves alterations in hormones secreted from glands in the brain. Genetic variations in these hormones can mean that some individuals are more susceptible to anxiety disorders. The aim of this observational study was to investigate possible relationships between genetic changes in brain hormones and anxiety in 72 individuals. The results showed that women were more likely than men to report feelings of anxiety and there were several relationships between genetic variations in brain hormones and self-reported measures of anxiety. It was concluded that genetic variations in brain hormones are associated with anxiety disorders in healthy individuals. This study could be used by healthcare professionals to understand how genetics could play a role in anxiety and that certain genes could be used to identify individuals at risk of anxiety disorders.
Abstract
BACKGROUND Two important aspects for the development of anxiety disorders are genetic predisposition and alterations in the hypothalamic-pituitary-adrenal (HPA) axis. In order to identify genetic risk-factors for anxiety, the aim of this exploratory study was to investigate possible relationships between genetic polymorphisms in genes important for the regulation and activity of the HPA axis and self-assessed anxiety in healthy individuals. METHODS DNA from 72 healthy participants, 37 women and 35 men, were included in the analyses. Their DNA was extracted and analysed for the following Single Nucleotide Polymorphisms (SNP)s: rs41423247 in the NR3C1 gene, rs1360780 in the FKBP5 gene, rs53576 in the OXTR gene, 5-HTTLPR in SLC6A4 gene and rs6295 in the HTR1A gene. Self-assessed anxiety was measured by the State and Trait Anxiety Inventory (STAI) questionnaire. RESULTS Self-assessed measure of both STAI-S and STAI-T were significantly higher in female than in male participants (p = 0.030 and p = 0.036, respectively). For SNP rs41423247 in the NR3C1 gene, there was a significant difference in females in the score for STAI-S, where carriers of the G allele had higher scores compared to the females that were homozygous for the C allele (p < 0.01). For the SNP rs53576 in the OXTR gene, there was a significant difference in males, where carriers of the A allele had higher scores in STAI-T compared to the males that were homozygous for the G allele (p < 0.01). CONCLUSION This study shows that SNP rs41423247 in the NR3C1 gene and SNP rs53576 in the OXTR gene are associated with self-assessed anxiety in healthy individuals in a gender-specific manner. This suggests that these SNP candidates are possible genetic risk-factors for anxiety.
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Plant Stanol Esters Reduce LDL (Low-Density Lipoprotein) Aggregation by Altering LDL Surface Lipids: The BLOOD FLOW Randomized Intervention Study.
Ruuth, M, Äikäs, L, Tigistu-Sahle, F, Käkelä, R, Lindholm, H, Simonen, P, Kovanen, PT, Gylling, H, Öörni, K
Arteriosclerosis, thrombosis, and vascular biology. 2020;(9):2310-2321
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Abstract
OBJECTIVE Plant stanol ester supplementation (2-3 g plant stanols/d) reduces plasma LDL (low-density lipoprotein) cholesterol concentration by 9% to 12% and is, therefore, recommended as part of prevention and treatment of atherosclerotic cardiovascular disease. In addition to plasma LDL-cholesterol concentration, also qualitative properties of LDL particles can influence atherogenesis. However, the effect of plant stanol ester consumption on the proatherogenic properties of LDL has not been studied. Approach and Results: Study subjects (n=90) were randomized to consume either a plant stanol ester-enriched spread (3.0 g plant stanols/d) or the same spread without added plant stanol esters for 6 months. Blood samples were taken at baseline and after the intervention. The aggregation susceptibility of LDL particles was analyzed by inducing aggregation of isolated LDL and following aggregate formation. LDL lipidome was determined by mass spectrometry. Binding of serum lipoproteins to proteoglycans was measured using a microtiter well-based assay. LDL aggregation susceptibility was decreased in the plant stanol ester group, and the median aggregate size after incubation for 2 hours decreased from 1490 to 620 nm, P=0.001. Plant stanol ester-induced decrease in LDL aggregation was more extensive in participants having body mass index<25 kg/m2. Decreased LDL aggregation susceptibility was associated with decreased proportion of LDL-sphingomyelins and increased proportion of LDL-triacylglycerols. LDL binding to proteoglycans was decreased in the plant stanol ester group, the decrease depending on decreased serum LDL-cholesterol concentration. CONCLUSIONS Consumption of plant stanol esters decreases the aggregation susceptibility of LDL particles by modifying LDL lipidome. The resulting improvement of LDL quality may be beneficial for cardiovascular health. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01315964.
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[Health hazards of physical inactivity].
Helajärvi, H, Lindholm, H, Vasankari, T, Heinonen, OJ
Duodecim; laaketieteellinen aikakauskirja. 2015;(18):1713-8
Abstract
Obesity and non-communicable diseases and related costs increase with physical inactivity. In addition to the lack of recreational exercise, a sedentary lifestyle also seems to have a negative effect of health, independently of other lifestyle and risks. New means, as well as multidisciplinary and multiprofessional collaboration, are required in order to improve health and well-being on the population level and to reduce health-related costs. New, more effective operational models are also needed in health communication in order to achieve the desired and more permanent results.
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Association between lowered endothelial function measured by peripheral arterial tonometry and cardio-metabolic risk factors - a cross-sectional study of Finnish municipal workers at risk of diabetes and cardiovascular disease.
Konttinen, J, Lindholm, H, Sinisalo, J, Kuosma, E, Halonen, J, Hopsu, L, Uitti, J
BMC cardiovascular disorders. 2013;:83
Abstract
BACKGROUND The aim of this cross-sectional study was to determine the association between lowered endothelial function measured by peripheral arterial tonometry (PAT) and cardio-metabolic risk factors. The study population consisted of Finnish municipal workers who were at risk of diabetes or cardiovascular disease and who had expressed a need to change their health behaviour. METHODS A total of 312 middle-aged municipal workers underwent a physical medical examination and anthropometry measurements. Levels of total cholesterol, HDL cholesterol, triglycerides, fasting glucose, glycated haemoglobin, and high sensitivity C-reactive protein were taken from the blood samples. PAT measured the increase in digital pulse volume amplitude during reactive hyperemia, and the index of endothelial function, F-RHI, was defined as the ratio of post-deflation amplitude to baseline amplitude. RESULTS In the linear regression model, male sex was associated with lower F-RHI. In sex-adjusted linear regression models, each of the variables; waist circumference, fasting glucose, glycated hemoglobin, triglycerides, body fat percentage, body mass index, current smoking, and impaired fasting glucose or diabetes were separately associated with lower F-RHI, and HDL cholesterol and resting heart rate were associated with higher F-RHI.HDL cholesterol, sex, body mass index, and current smoking entered a stepwise multivariable regression model, in which HDL cholesterol was associated with higher F-RHI, and smoking, male sex and body mass index were associated with lower F-RHI. This model explains 28.3% of the variability in F-RHI. CONCLUSIONS F-RHI is associated with several cardio-metabolic risk factors; low level of HDL cholesterol, male sex, overweight and smoking being the most important predictors of a lowered endothelial function. A large part of variation in F-RHI remains accounted for by unknown factors.
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12 weeks' aerobic and resistance training without dietary intervention did not influence oxidative stress but aerobic training decreased atherogenic index in middle-aged men with impaired glucose regulation.
Venojärvi, M, Korkmaz, A, Wasenius, N, Manderoos, S, Heinonen, OJ, Lindholm, H, Aunola, S, Eriksson, JG, Atalay, M
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 2013;:127-35
Abstract
Our aim was to determine whether 12 weeks' aerobic Nordic walking (NW) or resistance exercise training (RT) without diet-induced weight loss could decrease oxidative stress and atherogenic index of plasma (AIP), prevalence of metabolic syndrome (MetS) and MetS score in middle-aged men with impaired glucose regulation (IGR) (n=144. 54.5 ± 6.5 years). In addition, we compared effects of intervention between overweight and obese subgroups. Prevalence of MetS and AIP index decreased only in NW group and MetS score in both NW and RT groups but not in control group. The changes in AIP index correlated inversely with changes in plasma antioxidant capacity. The change in AIP index remained a significant independent predictor of the changes in MetS score after the model was adjusted for age, BMI and volume of exercise (MET h/week) in NW group. There were no changes in the other measured markers of oxidative stress and related cytokines (e.g. osteopontin and osteoprotegerin) in any of the groups. Nordic walking decreased prevalence of MetS and MetS score. Improved lipid profile remained a predictor of decreased MetS score only in NW group and it seems that Nordic walking has more beneficial effects on cardiovascular disease risks than RT training.
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Nordic walking decreased circulating chemerin and leptin concentrations in middle-aged men with impaired glucose regulation.
Venojärvi, M, Wasenius, N, Manderoos, S, Heinonen, OJ, Hernelahti, M, Lindholm, H, Surakka, J, Lindström, J, Aunola, S, Atalay, M, et al
Annals of medicine. 2013;(2):162-70
Abstract
BACKGROUND Dysfunction of adipose tissue is one of the major factors leading to insulin resistance. Altered adipokine concentration is an early sign of adipose tissue dysfunction. The aim of this study was to assess the impact of exercise intervention on adipokine profile, glycemic control, and risk factors of the metabolic syndrome (MeS) in men with impaired glucose regulation (IGR). METHODS Overweight and obese men with IGR (n =144) aged 40-65 years were studied at baseline and at 12 weeks in a randomized controlled multicenter intervention study. BMI varied from 25.1 to 34.9. The subjects were randomized into one of three groups: 1) a control group (C; n =47), 2) a Nordic walking group (NW; n =48), or 3) a resistance training group (RT; n =49). RESULTS Leptin concentrations decreased in the NW group compared to both other groups. Both types of exercise intervention significantly decreased serum chemerin concentrations compared to the C group. In the NW group also body fat percentage, fatty liver index (FLI), and total and LDL cholesterol concentrations decreased compared to the RT group. CONCLUSIONS Nordic walking intervention seems to decrease chemerin and leptin levels, and subjects in this intervention group achieved the most beneficial effects on components of MeS.