| 1. |
|
|
| 2. |
- Hagforsen, Eva, et al.
(författare)
-
Calcium homeostasis and body composition in patients with palmoplantar pustulosis : a case-control study
- 2012
-
Ingår i: British Journal of Dermatology. - : Oxford University Press (OUP). - 0007-0963 .- 1365-2133. ; 166:1, s. 74-81
-
Tidskriftsartikel (refereegranskat)abstract
- Background Palmoplantar pustulosis (PPP) is a common disease strongly associated with smoking, autoimmune comorbidities and a deranged calcium homeostasis. It is unclear whether these changes in calcium homeostasis are a consequence of vitamin D status, abnormal dermal vitamin D synthesis or whether they are substantiated in effects on bone mineral density (BMD). Objectives To study the vitamin D status and BMD in patients with PPP. Methods In comparisons with two sets of controls (n = 101 for serum analyses and n = 5123 for BMD analyses), we therefore aimed to investigate whether PPP (59 cases) was associated with serum levels of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, whether patients with PPP had decreased BMD and finally if the dermal expression of 25-hydroxyvitamin D(3) -1α-hydroxylase (CYP27B1) and the vitamin D receptor (VDR) were affected in PPP skin lesions. Results We found no differences in mean serum 25-hydroxyvitamin D levels between cases and controls, whereas PPP cases displayed 17·8 pmol L(-1) lower (P = 0·04) values in 1,25-dihydroxyvitamin D. BMD at the hip, lumbar spine or of total body did not differ substantially between cases and controls. Finally, patients with PPP had lower dermal expression of CYP27B1 and VDR in affected skin lesions. Conclusions The increase in serum calcium levels and suppressed parathyroid hormone in patients with PPP were not attributable to derangements in vitamin D status and these patients did not have lower BMD.
|
|
| 3. |
- Hagforsen, Eva, et al.
(författare)
-
Women with palmoplantar pustulosis have disturbed calcium homeostasis and a high prevalence of diabetes mellitus and psychiatric disorders : a case-control study
- 2005
-
Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 85:3, s. 225-232
-
Tidskriftsartikel (refereegranskat)abstract
- Palmoplantar pustulosis is characterized by pustule formation in the acrosyringium. Nearly 50% of palmoplantar pustulosis sera produce immunofluorescence of the palmar papillary endothelium from healthy subjects, but also of the endothelium of normal parathyroid gland. With a case-control design the levels of calcium and parathyroid hormone in serum were measured in 60 women with palmoplantar pustulosis and 154 randomly selected population-based control women. One-third of the controls had been smokers, whereas 95% of the cases were or had been smokers. Mean age-adjusted serum calcium was increased in the patients compared with the controls (2.43 vs 2.36 mmol/l; p<0.0001), whereas the parathyroid hormone concentration was suppressed (23.2 vs 31.1 ng/l; p<0.0001). The plasma levels of parathyroid hormone-related protein were normal in patients but there was a strong expression of this protein in the acrosyringium both in palmoplantar pustulosis and control skin. As even a marginal elevation of serum calcium is associated with an increased risk for diabetes, cardiovascular disease and psychiatric disease, we analysed the risk for these disorders in palmoplantar pustulosis patients compared with that in the control group. Both diabetes mellitus and psychiatric disorders were associated with palmoplantar pustulosis with an odds ratio of 8.7 (95% CI 3.3-22.8) and 5.6 (95% CI 2.2-14.4), respectively. Palmoplantar pustulosis is a complex disease with an increased risk for several non-dermatological disorders. The role of the mildly increased serum calcium for the high risk for diabetes and depression deserves to be studied.
|
|
| 4. |
- Hallberg, Pär, et al.
(författare)
-
Adipocyte-derived leucine aminopeptidase genotype and response to antihypertensive therapy
- 2003
-
Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261 .- 1471-2261. ; 18:3, s. 11-
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundAdipocyte-derived leucine aminopeptidase (ALAP) is a recently identified member of the M1 family of zinc-metallopeptidases and is thought to play a role in blood pressure control through inactivation of angiotensin II and/or generation of bradykinin. The enzyme seems to be particularly abundant in the heart. Recently, the Arg528-encoding allele of the ALAP gene was shown to be associated with essential hypertension.MethodsWe evaluated the influence of this polymorphism on the change in left ventricular mass index in 90 patients with essential hypertension and echocardiographically diagnosed left ventricular hypertrophy, randomised in a double-blind study to receive treatment with either the angiotensin II type I receptor antagonist irbesartan or the beta1-adrenoceptor blocker atenolol for 48 weeks. Genyotyping was performed using minisequencing.ResultsAfter adjustment for potential covariates (blood pressure and left ventricular mass index at baseline, blood pressure change, age, sex, dose and added antihypertensive treatment), there was a marked difference between the Arg/Arg and Lys/Arg genotypes in patients treated with irbesartan; those with the Arg/Arg genotype responded on average with an almost two-fold greater regression of left ventricular mass index than patients with the Lys/Arg genotype (-30.1 g/m2 [3.6] vs -16.7 [4.5], p = 0.03).ConclusionsThe ALAP genotype seems to determine the degree of regression of left ventricular hypertrophy during antihypertensive treatment with the angiotensin II type I receptor antagonist irbesartan in patients with essential hypertension and left ventricular hypertrophy. This is the first report of a role for ALAP/aminopeptidases in left ventricular mass regulation, and suggests a new potential target for antihypertensive drugs.
|
|
| 5. |
- Jiang, X., et al.
(författare)
-
Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels
- 2018
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
-
Tidskriftsartikel (refereegranskat)abstract
- Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7x10(-9) at rs8018720 in SEC23A, and P = 1.9x10(-14) at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene-gene interactions in the heritability of circulating 25-hydroxyvitamin D levels.
|
|
| 6. |
- Karasik, D., et al.
(författare)
-
Disentangling the genetics of lean mass
- 2019
-
Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 109:2, s. 276-287
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Lean body mass (LM) plays an important role in mobility and metabolic function. We previously identified five loci associated with LM adjusted for fat mass in kilograms. Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass. Objectives: To determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci. Methods: We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age(2), and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms). Results: Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts. Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R). In contrast, loci with an impact specifically on LMwere termed "body builder" loci (VCAN and ADAMTSL3). Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection. Conclusions: In conclusion, we identified one novel LM locus (TNRC6B). Our results suggest that a genetically determined increase in lean mass might exert either harmful or protective effects on metabolic traits, depending on its relation to fat mass.
|
|
| 7. |
- Maddock, Jane, et al.
(författare)
-
Vitamin D and cognitive function : A Mendelian randomisation study.
- 2017
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- The causal nature of the association between hypovitaminosis D and poor cognitive function in mid- to later-life is uncertain. Using a Mendelian randomisation(MR) approach, we examined the causal relationship between 25(OH)D and cognitive function. Data came from 172,349 participants from 17 cohorts. DHCR7(rs12785878), CYP2R1 rs12794714) and their combined synthesis score were chosen to proxy 25(OH)D. Cognitive tests were standardised into global and memory scores. Analyses were stratified by 25(OH)D tertiles, sex and age. Random effects meta-analyses assessed associations between 25(OH)D and cognitive function. Associations of serum 25(OH)D with global and memory-related cognitive function were non-linear (lower cognitive scores for both low and high 25(OH)D, p curvature ≤ 0.006), with much of the curvature attributed to a single study. DHCR7, CYP2R1, and the synthesis score were associated with small reductions in 25(OH)D per vitamin D-decreasing allele. However, coefficients for associations with global or memory-related cognitive function were non-significant and in opposing directions for DHCR7 and CYP2R1, with no overall association observed for the synthesis score. Coefficients for the synthesis score and global and memory cognition were similar when stratified by 25(OH)D tertiles, sex and age. We found no evidence for serum 25(OH)D concentration as a causal factor for cognitive performance in mid- to later life.
|
|
| 8. |
- Michaëlsson, Madeleine, 1968-, et al.
(författare)
-
The impact and causal directions for the associations between diagnosis of ADHD, socioeconomic status, and intelligence by use of a bi-directional two-sample Mendelian randomization design
- 2022
-
Ingår i: BMC Medicine. - : BioMed Central (BMC). - 1741-7015. ; 20:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background Previous studies have reported associations between attention-deficit/hyperactivity disorder (ADHD) and lower socioeconomic status and intelligence. We aimed to evaluate the causal directions and strengths for these associations by use of a bi-directional two-sample Mendelian randomization (MR) design. Methods We used summary-level data from the largest available genome-wide association studies (GWAS) to identify genetic instruments for ADHD, intelligence, and markers of socioeconomic status including the Townsend deprivation index, household income, and educational attainment. Effect estimates from individual genetic variants were combined using inverse-variance weighted regression. Results A genetically predicted one standard deviation (SD) increment in the Townsend deprivation index conferred an odds ratio (OR) of 5.29 (95% confidence interval (CI) 1.89-14.76) for an ADHD diagnosis (p<0.001). A genetically predicted one SD higher education level conferred an OR of 0.30 (95% CI 0.25-0.37) (p<0.001), and a genetically predicted one SD higher family income provided an OR of 0.35 (95% CI 0.25-0.49; p<0.001). The associations remained after adjustment for intelligence whereas the lower odds of an ADHD diagnosis with higher intelligence did not persist after adjustment for liability to greater educational attainment (adjusted OR 1.03, 95% CI 0.68-1.56; p=0.87). The MR analysis of the effect of ADHD on socioeconomic markers found that genetic liability to ADHD was statistically associated with each of them (p<0.001) but not intelligence. However, the average change in the socioeconomic markers per doubling of the prevalence of ADHD corresponded only to 0.05-0.06 SD changes. Conclusions Our results indicate that an ADHD diagnosis may be a direct and strong intelligence-independent consequence of socioeconomic related factors, whereas ADHD appears to lead only to modestly lowered socioeconomic status. Low intelligence seems not to be a major independent cause or consequence of ADHD.
|
|
| 9. |
- Nordström, Peter, et al.
(författare)
-
Geriatric Rehabilitation and Discharge Location After Hip Fracture in Relation to the Risks of Death and Readmission
- 2016
-
Ingår i: Journal of the American Medical Directors Association. - : Elsevier. - 1525-8610 .- 1538-9375. ; 17:1
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To investigate the effects of geriatric rehabilitation on short-term risk of death and readmission after a hip fracture were investigated in a nationwide cohort. In addition, the association of discharge location (nursing home or patient's home) with the short-term risk of death was assessed.DESIGN, SETTING, AND PARTICIPANTS: The cohort consisted of 89,301 individuals at least 50 years of age, with a first hip fracture registered in the Swedish quality register RIKSHÖFT, the years 2004-2012.MEASURES: Short-term risk of death and readmission to hospital after discharge was compared at 8 hospitals, where most patients received inpatient care in geriatric wards, and those treated at 71 regular hospitals.RESULTS: The risks of death within 30 days of admission were 7.1% in patients admitted to geriatric ward hospitals and 7.4% in those treated at regular hospitals (multivariable-adjusted hazard ratio [HR] 0.91, 95% CI 0.85-0.97), whereas the odds of readmission within 30 days of discharge were 8.7% and 9.8%, respectively (multivariable-adjusted odds ratio 0.86, 95% CI 0.81-0.91). The risk of death was influenced by discharge location and inpatient length of stay (LOS). Thus, for patients discharged to short-term nursing homes with a LOS of at most 10 days, each additional day of LOS reduction increased the risk of death within 30 days of discharge by 13% (HR 1.13, 95% CI 1.08-1.18). This association was reduced in patients discharged to permanent nursing homes (HR 1.04, 95% CI 1.02-1.07), and not significant in those discharged to their own home (OR 1.00, 95% CI 0.91-1.10).CONCLUSION: The risks of death and readmission were lower in patients with hip fracture who received care in hospitals with geriatric wards. The risk of death after discharge increased with shorter LOS, especially in patients discharged to short-term nursing homes.
|
|
| 10. |
- Stattin, Karl, et al.
(författare)
-
Decreased hip, lower leg and humeral fractures but increased forearm fractures in highly active individuals
- 2018
-
Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 33:10, s. 1842-1850
-
Tidskriftsartikel (refereegranskat)abstract
- It is not known how physical exercise affects the risk of different types of fractures, especially in highly active individuals. To investigate this association, we studied a cohort of 118,204 men and 71,757 women who from 1991 to 2009 participated in Vasaloppet, a long-distance cross-country skiing race in Sweden, and 505,194 nonparticipants frequency-matched on sex, age, and county of residence from the Swedish population. Participants ranged from recreational exercisers to world-class skiers. Race participation, distance of race run, number of races participated in, and finishing time were used as proxies for physical exercise. Incident fractures from 1991 to 2010 were obtained from national Swedish registers. Over a median follow-up of 8.9 years, 53,175 fractures of any type, 2929 hip, 3107 proximal humerus, 11,875 lower leg, 11,733 forearm, and 2391 vertebral fractures occurred. In a Cox proportional hazard regression analysis using time-updated exposure and covariate information, participation in the race was associated with an increased risk of any type of fracture (hazard ratio [HR], 1.02; 95% CI, 1.00 to 1.05); forearm fractures had an HR, 1.11 with a 95% CI, 1.06 to 1.15. There was a lower risk of hip (HR, 0.75; 95% CI, 0.67 to 0.83), proximal humerus (HR, 0.90; 95% CI, 0.82 to 0.98), and lower leg fractures (HR, 0.93; 95% CI, 0.89 to 0.97), whereas the HR of vertebral fracture was 0.97 with a 95% CI, 0.88 to 1.07. Among participants, the risk of fracture was similar irrespective of race distance and number of races run. Participants close to the median finishing time had a lower risk of fracture compared with faster and slower participants. In summary, high levels of physical exercise were associated with a slightly higher risk of fractures of any type, including forearm fractures, but a lower risk of hip, proximal humerus, and lower leg fractures.
|
|
