Publications

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Hyperprolactinemia is a common side-effect of antipsychotic treatment. Antipsychotics and hyperprolactinemia are both considered risk factors of metabolic disturbances and diabetes. Investigations on prolactin response to meal ingestion in antipsychotic-treated patients are missing. In a case-control design, 49 antipsychotic-treated, clinically stable, non-diabetic, schizophrenia spectrum male patients were compared with 93 healthy male controls by age (33.1, SD 7.4 vs. 32.9, SD 6.6 years), body mass index (26.2, SD 4.6 vs. 26.1, SD 3.9kg/m(2)) and waist circumference (96.4, SD 13.0 vs. 96.7, SD 11.9cm). Serum-prolactin was measured in the morning and 90min after ingestion of a standardized liquid meal (2268kJ). Fasting prolactin levels varied considerably, and mean fasting prolactin levels did not significantly differ between patients and controls (12.33, SD 11.58 vs. 10.06, SD 8.67ng/ml, p=0.623). In the controls, postprandial serum prolactin was significantly reduced (Δ -2.53, SD 9.75ng/ml, p=0.016). In antipsychotic-treated patients postprandial serum prolactin tended to increase (Δ 2.62, SD 10.96ng/ml, p=0.081). Analyses of subgroups based on the prolactinogenic liability of their antipsychotic treatment indicated 22 to 65% higher postprandial prolactin levels with high and intermediate prolactinogenic antipsychotics. A physiological postprandial suppression of serum prolactin appears absent in antipsychotic-treated males. Marked variability in fasting prolactin levels may reflect individual variations in the diurnal cycle. Uniform acquisition procedures accounting for diurnal variation and food intake may enhance reliability of prolactin levels in antipsychotic-treated male patients. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
    Psychoneuroendocrinology 06/2015; 20. DOI:10.1016/j.psyneuen.2015.05.014 · 5.59 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Epidermal filaggrin deficiency due to common filaggrin gene (FLG) mutations causes xerosis and strongly increases the risk of atopic dermatitis and even asthma. However, it is unknown whether xerosis independent of FLG mutations could also increase the risk of asthma. To evaluate whether generalized xerosis was associated with asthma, independent of atopic dermatitis and common FLG mutations in a cross-sectional study on adult Danes. A total of 3396 adults from the general population participated in a health examination. Lung function and serum-specific IgE levels to inhalant allergens were measured and information on xerosis and atopic diseases was obtained by means of a questionnaire. Participants were genotypes for the three most common FLG mutations in Northern Europeans: R501X, 2282del4 and R2447X. Fully adjusted logistic regression analyses showed that asthma (either current or at some point in life) was significantly associated with reporting generalized xerosis (OR 1.32; 95% CI 1.02-1.72). The association was stronger in men (OR 1.79; 95% CI 1.13-2.84) when compared to women (OR 1.18; 95% CI 0.86-1.62). Furthermore, a significant association was observed between xerosis and 'allergic asthma' in men (OR 2.13; 95% CI 1.08-4.19). Our findings indicate an association between xerosis and asthma in men independent of atopic dermatitis and FLG mutations. Both facilitated allergen sensitization and secondary degradation of filaggrin following T-helper cell 2 inflammation might be key elements to understanding this relationship. © 2015 European Academy of Dermatology and Venereology.
    Journal of the European Academy of Dermatology and Venereology 02/2015; DOI:10.1111/jdv.13051 · 3.11 Impact Factor
  • Source
    Journal of Allergy and Clinical Immunology 02/2015; 135(5). DOI:10.1016/j.jaci.2015.01.001 · 11.25 Impact Factor
  • Source
    Journal of the European Academy of Dermatology and Venereology 11/2014; DOI:10.1111/jdv.12821 · 3.11 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To date, treatment of hypertriglyceridemia with long-chain n-3 polyunsaturated fatty acids (n-3 PUFA) has been investigated solely in fasting and postprandial subjects. However, non-fasting triacylglycerols are more strongly associated with risk of cardiovascular disease. The objective of this study was to investigate the effect of long-chain n-3 PUFA on non-fasting triacylglycerol levels and to compare the effects of n-3 PUFA formulated as acylglycerol (AG-PUFA) or ethyl esters (EE-PUFA). The study was a double-blinded randomized placebo-controlled interventional trial, and included 120 subjects with non-fasting plasma triacylglycerol levels of 1.7-5.65 mmol/L (150-500 mg/dL). The participants received approximately 3 g/day of AG-PUFA, EE-PUFA, or placebo for a period of eight weeks. The levels of non-fasting plasma triacylglycerols decreased 28 % in the AG-PUFA group and 22 % in the EE-PUFA group (P < 0.001 vs. placebo), with no significant difference between the two groups. The triacylglycerol lowering effect was evident after four weeks, and was inversely correlated with the omega-3 index (EPA + DHA content in erythrocyte membranes). The omega-3 index increased 63.2 % in the AG-PUFA group and 58.5 % in the EE-PUFA group (P < 0.001). Overall, the heart rate in the AG-PUFA group decreased by three beats per minute (P = 0.045). High-density lipoprotein (HDL) cholesterol increased in the AG-PUFA group (P < 0.001). Neither total nor non-HDL cholesterol changed in any group. Lipoprotein-associated phospholipase A2 (LpPLA2) decreased in the EE-PUFA group (P = 0.001). No serious adverse events were observed. Supplementation with long-chain n-3 PUFA lowered non-fasting triacylglycerol levels, suggestive of a reduction in cardiovascular risk. Regardless of the different effects on heart rate, HDL, and LpPLA2 that were observed, compared to placebo, AG-PUFA, and EE-PUFA are equally effective in reducing non-fasting triacylglycerol levels.
    Lipids 11/2014; 50(2). DOI:10.1007/s11745-014-3968-6 · 2.35 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Treatment with antipsychotic drugs is widely associated with metabolic side effects such as weight gain and disturbed glucose metabolism, but the pathophysiologic mechanisms are unclear.
    Schizophrenia Research 09/2014; 75(9):e899-e905. DOI:10.4088/JCP.13m08820 · 4.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective To establish reference intervals for cancer antigen 125 (CA-125) in women with expected normal pregnancy, delivery and early postpartum period.DesignProspective observational study.SettingDepartment of Clinical Biochemistry and Obstetrics, Copenhagen University Hospital, Gentofte, Denmark.PopulationA total of 801 women with expected normal pregnancies were investigated. Of these, 640 delivered vaginally, 82 by emergency cesarean section, and 79 by elective cesarean section; 720 women had uncomplicated pregnancies.Methods Samples were collected at gestational weeks 13-20, 21-28, 29-34, and 35-42 during labor and on first and second day postpartum. Reference intervals were calculated for each gestational period as recommended by the International Federation of Clinical Chemistry and Laboratory Medicine.Main outcome measureConcentration of serum CA-125 during the gestational period and around delivery.ResultsCA-125 was fairly stable below 35 U/mL during pregnancy, but increased markedly during vaginal delivery, to a minor degree during emergency cesarean section, and only slightly during elective cesarean section. In the early postpartum period, CA-125 decreased with an apparent half-life of 24 hours.Conclusions The CA-125 cut-off value (< 35 U/mL) used for non-pregnant women can be used for women during pregnancy after gestational week 13 as a supplement to ultrasound evaluation of ovarian cysts. The wide range of CA-125 concentration during normal pregnancies makes it unlikely that small fluctuations in CA-125 can be clinically useful for identifying other conditions. Measuring CA-125 around the time of delivery is not recommended. Gestational age-specific reference intervals during normal pregnancy are not needed.This article is protected by copyright. All rights reserved.
    Acta Obstetricia Et Gynecologica Scandinavica 08/2014; 93(12). DOI:10.1111/aogs.12492 · 1.99 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Purpose Filaggrin proteins are expressed in the skin, oral cavity, oesophagus, and cervical mucose. Loss-of-function mutations in the filaggrin gene (FLG) reduce filaggrin expression and cause an impaired skin barrier function. We hypothesized that FLG mutation carriers would be more susceptible to human papillomavirus (HPV) infection and thus a higher risk of HPV-related cancer and pre-cancer. We investigated the association of the FLG genotype with incidence of HPV-related cancer of cervix, vagina, vulva, penis, anus and head and neck, and pre-cancer of the cervix. Methods We included 13,376 persons from four population-based studies conducted in the same background population in Copenhagen, Denmark. Participants were genotyped for the most common FLG mutations in Europeans. Information on cancer was obtained from The Danish Cancer Registry until 11 July 2011. Results There were 489 cases of prevalent and 97 cases of incident HPV-related cancer and pre-cancer (median follow-up 11.5 years). There was a statistically significant association between FLG genotype and incident HPV-related cancer and pre-cancer with a hazard ratio, HR = 2.1 (95% confidence intervals, CI: 1.2, 3.7) for FLG mutation carriers vs. wild types. Conclusions FLG loss-of-function mutations were associated with higher incidence of HPV-related cancers and pre-cancers that are potentially screening and vaccine preventable.
    PLoS ONE 06/2014; 9(6):e99437. DOI:10.1371/journal.pone.0099437 · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Loss-of-function mutations in the filaggrin gene (FLG) could have opposing effects on cancer risk, since mutations are both associated with 10% higher serum vitamin D levels, which are possibly protective against cancer, and with impaired skin barrier function, which could lead to a higher cancer susceptibility.Objectives We investigated the association of the FLG genotype and specific types of cancers in four population-based cohorts.MethodsA total of 13,376 individuals were included and genotyped for selected common FLG mutations in Northern Europeans. Information on cancer was obtained from The Danish Cancer Registry until 11 July 2011. Persons with a history of cancer at baseline were excluded from the prospective analyses.ResultsThere were 1,339 incident cancers (median follow-up 11.4 years). The hazard ratios (HRs) and 95% confidence intervals, (95% CIs) for FLG mutation carriers vs. wild types were: for any cancer (HR=0.95, 95% CI: 0.78, 1.16), any cancer excluding non-melanoma skin cancer (NMSC) (HR=1.05, 95% CI: 0.84, 1.31), head and neck cancer (HR=1.72, 95% CI: 0.71, 4.15), colorectal cancer (HR=0.82, 95% CI: 0.44, 1.52), cancer of bronchus and lung (HR=1.34, 95% CI: 0.77, 2.33), breast cancer (HR=0.58, 95% CI: 0.30, 1.14), cancer of the uterus (HR=0.42, 95% CI: 0.06, 3.10), prostate cancer (HR=1.09, 95% CI: 0.61, 1.94), urinary cancer (HR=1.30, 95% CI: 0.51, 3.29), malignant melanoma (HR=1.03, 95% CI: 0.41, 2.58) and NMSC (HR=0.70, 95% CI: 0.47, 1.05). In subgroup analyses of the participants over the age of 60 years at baseline, we found statistically significant lower risks of all cancers and NMSC among FLG mutation carriers.Conclusions There were no statistically significant associations between FLG loss-of-function mutations and cancer except in subgroup analyses.This article is protected by copyright. All rights reserved.
    British Journal of Dermatology 03/2014; 171(6). DOI:10.1111/bjd.12969 · 4.10 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Loss-of-function mutations in the filaggrin gene (FLG) are observed in approximately 10% of Northern Europeans. Heterozygous and homozygous mutation-carriers have, respectively, partial or complete reduction of epidermal filaggrin and its degradation products. Among others, filaggrin is degraded to trans-urocanic acid (UCA)(1) ; a chromophore that provides protection against ultraviolet (UV) radiation and modulates cutaneous immune functions(1) . This article is protected by copyright. All rights reserved.
    British Journal of Dermatology 02/2014; DOI:10.1111/bjd.12911 · 4.10 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Multiple chemical sensitivity (MCS) is a medically unexplained condition characterized by reports of recurrent unspecific symptoms attributed to exposure to low levels of common volatile chemicals. The etiology of MCS is poorly understood, but dysregulation of the immune system has been proposed as part of the pathophysiology. Objective To compare plasma levels of cytokines in Danish MCS individuals with a healthy, sex- and age-matched control group. Method Blood samples were obtained from 150 un-exposed MCS individuals and from 148 age- and sex-matched healthy controls. Plasma concentrations of 14 cytokines, chemokines and growth and allergen-specific IgE were measured. All participants completed a questionnaire including questions on MCS, psychological distress, morbidities and medication use at the time of the study. Results Plasma levels of interleukin-1β, -2, -4, and -6 were significantly (P < 0.001) increased in the MCS group compared with controls, tumor necrosis factor-α was borderline significantly (P = 0.05) increased and interleukin-13 was significantly decreased (P < 0.001). Conclusion MCS individuals displayed a distinct systemic immune mediator profile with increased levels of pro-inflammatory cytokines and interleukin-2 and inverse regulation of Th2 associated cytokines interleukin-4 and interleukin-13 suggestive of low-grade systemic inflammation, along with a deviating Th2-associated cytokine response not involving IgE-mediated mechanisms.
    Psychoneuroendocrinology 02/2014; 40:140–150. DOI:10.1016/j.psyneuen.2013.11.012 · 5.59 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Anti-nuclear antibodies (ANA) have traditionally been evaluated using indirect fluorescence assays (IFA) with HEp-2 cells. Quantitative immunoassays (EIA) have replaced the use of HEp-2 cells in some laboratories. Here, we evaluated ANA in 400 consecutive and unselected routinely referred patients using IFA and automated EIA techniques. The IFA results generated by two independent laboratories were compared with the EIA results from antibodies against double-stranded DNA (dsDNA), from ANA screening, and from tests of the seven included subantigens. The final IFA and EIA results for 386 unique patients were compared. The majority of the results were the same between the two methods (n = 325, 84%); however, 8% (n = 30) yielded equivocal results (equivocal-negative and equivocal-positive) and 8% (n = 31) yielded divergent results (positive-negative). The results showed fairly good agreement, with Cohen's kappa value of 0.30 (95% confidence interval (CI) = 0.14-0.46), which decreased to 0.23 (95% CI = 0.06-0.40) when the results for dsDNA were omitted. The EIA method was less reliable for assessing nuclear and speckled reactivity patterns, whereas the IFA method presented difficulties detecting dsDNA and Ro activity. The automated EIA method was performed in a similar way to the conventional IFA method using HEp-2 cells; thus, automated EIA may be used as a screening test.
    01/2014; 2014:534759. DOI:10.1155/2014/534759
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Common loss-of-function mutations in the filaggrin gene (FLG) are a major predisposing risk factor for atopic disease due to reduced epidermal filaggrin protein levels. We previously observed an association between these mutations and type 2 diabetes and hypothesized that an inherited impairment of skin barrier functions could facilitate low-grade inflammation and hence increase the risk of diabetes and cardiovascular disease. We examined the association between loss-of-function mutations in FLG and diabetes, stroke, ischemic heart disease (IHD), and all-cause mortality in the general population. The R501X and 2282del4 loss-of function mutations in FLG were genotyped in four Danish study populations including a total of 13373 adults aged 15-77 years. Two of the studies also genotyped the R2447X mutation. By linkage to Danish national central registers we obtained information for all participants on dates of diagnoses of diabetes, stroke, and IHD, as well as all-cause mortality. Data were analyzed by Cox proportional hazard models and combined by fixed effect meta-analyses. In meta-analyses combining the results from the four individual studies, carriage of loss-of-function mutations in FLG was not associated with incident diabetes (hazard ratio (HR) (95% confidence intervals (CI)) = 0.95 (0.73, 1.23), stroke (HR (95% CI) = 1.27 (0.97, 1.65), ischemic heart disease (HR (95%CI) = 0.92 (0.71, 1.19), and all-cause mortality (HR (95%CI) = 1.02 (0.83, 1.25)). Similar results were obtained when including prevalent cases in logistic regression models. Our results suggest that loss-of-function mutations in FLG are not associated with type 2 diabetes, cardiovascular disease, and all-cause mortality. However, larger studies with longer follow-up are needed to exclude any associations.
    PLoS ONE 12/2013; 8(12):e84293. DOI:10.1371/journal.pone.0084293 · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background/Objectives:The aim was to examine the causal effect of vitamin D on serum adiponectin using a multiple instrument Mendelian randomization approach.Subjects/Methods:Serum 25-hydroxy vitamin D (25(OH)D) and serum total or high molecular weight (HMW) adiponectin were measured in two Danish population-based studies: the Inter99 study (6405 adults, 30-60 years) conducted in 1999-2001, and the MONICA10 study (2656 adults, 41-71 years) conducted in 1993-1994.Results:In the Inter99 study, serum 25(OH)D was positively associated with total adiponectin (the effect estimate in % per doubling of 25(OH)D was 4.78, 95% CI: 1.96, 7.68, P<0.001). Using variations in the vitamin D-binding protein gene and the filaggrin gene as instrumental variables, the causal effect in % was estimated to 61.46, 95% CI: 17.51, 120.28, P=0.003 higher adiponectin per doubling of 25(OH)D. In the MONICA10 cohort, no significant association was observed between the serum concentrations of 25(OH)D and HMW adiponectin (the effect estimate in % per doubling of 25(OH)D was -1.51, 95% CI: -5.80, 2.98, P=0.50), although the instrumental variables analysis to some extent supported a positive causal association (the effect estimate in % per doubling of 25(OH)D was 37.13, 95% CI: -3.67, 95.20, P=0.080).Conclusions:The results indicate a possible causal association between serum 25(OH)D and total adiponectin. However, the association was not replicated for HMW adiponectin. Thus, further studies are needed to confirm a causal relationship.European Journal of Clinical Nutrition advance online publication, 13 November 2013; doi:10.1038/ejcn.2013.233.
    European journal of clinical nutrition 11/2013; 68(2). DOI:10.1038/ejcn.2013.233 · 2.95 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: More than 40 null mutations in the filaggrin (FLG) gene are described. It is therefore possible to find two different null mutations in one individual (compound heterozygosity). It has been generally perceived that homozygous and compound heterozygous individuals were genotypically comparable; however, this has not been scientifically investigated. Two different FLG null mutations in the same individual may be in trans position, meaning that each mutation locates to a different allele functionally equivalent to homozygosity, or may be in cis position, meaning that both mutations locate to the same allele functionally equivalent to heterozygosity. To experimentally investigate allelic in cis versus in trans configuration of the two most common filaggrin (FLG) mutations (R501X and 2282del4) in compound heterozygous individuals. Testing for in cis or in trans allele configuration was performed by means of allele-specific PCR amplification and analysis of PCR products by agarose gel electrophoresis. All R501X/2282del4 compound heterozygous samples collected over a 4-year period of routine FLG mutation testing were investigated. In total, 37 samples were tested. All thirty-seven R501X/2282del4 compound heterozygous individuals were found to carry the two mutations in trans position. FLG null mutation compound heterozygous individuals can be considered functionally equivalent to FLG null mutation homozygosity for any of the two mutations.
    Experimental Dermatology 09/2013; 22(9):572-5. DOI:10.1111/exd.12199 · 4.12 Impact Factor
  • Source
    Pal B Szecsi, Steen Stender
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Specific immunoglobulin E (IgE) antibody in vitro tests are performed on enzyme immunoassay systems. Poor agreement among systems has been reported and comparisons have been made exclusively with allergen extracts - not with recombinant allergens. Here we compare the ImmunoCAP and the IMMULITE systems. Methods: Ten patient samples with positive IgE toward egg white, birch pollen or cat or dog dander were compared using allergen extracts or the recombinant allergens Gal d 1, Bet v 1, Fel d 1 and Can f 1 with the two assay systems. Comparisons were also performed using four monoclonal mouse-human chimeric IgE antibodies specific for the same allergenic components. Results: IMMULITE estimated a higher allergen-specific IgE concentration in sera than ImmunoCAP when testing with allergen extracts as well as recombinant allergens. The chimeric antibodies gave an equivalent response in the total IgE and specific IgE (sIgE) with an average ratio of 1.08 (range 0.9-1.3) on ImmunoCAP. In contrast, IMMULITE exhibited sIgE signals that were substantially higher than the summed level of IgE for all four chimeric antibodies (average ratio 2.96 and range 1.7-4.3). Conclusion: Comparison using chimeric antibodies allowed the evaluation of the true performance of the systems. ImmunoCAP measured total IgE and sIgE equally, whereas IMMULITE displayed higher sIgE signals when compared to the summed level of total IgE for all four chimeric antibodies. Results obtained with the two assay systems are not interchangeable by means of mathematical conversion.
    International Archives of Allergy and Immunology 07/2013; 162(2):33-36. DOI:10.1159/000353276 · 2.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Loss-of-function mutations in the filaggrin gene (FLG) are associated with xerosis, atopic dermatitis, and early onset of hand eczema. Irritant exposure is a risk factor for occupational hand eczema, and FLG mutations increase the risk of occupational irritant contact dermatitis on the hands in hospital cohorts. It is unknown whether FLG mutations affect the level of irritant exposure. To evaluate whether exposure to occupational irritants was dependent on FLG mutations, atopic dermatitis, and age at hand eczema onset. Randomly chosen Danish adults completed a questionnaire on general health and occupational exposures. Genotyping for FLG mutations (R501X, 2282del4, and R2447X) and patch testing were performed. Overall, 38.7% of subjects reported present or previous occupational exposure to irritants. Among individuals who reported hand eczema onset before entering their work life, 50.6% (45/89) of FLG non-mutation carriers became exposed to irritants, as compared with 28.6% (4/14) of heterozygous and 0% (0/6) of homozygous mutation carriers (p = 0.006). Avoidance was conspicuous among mutation carriers reporting childhood hand eczema and atopic dermatitis (odds ratio 0.08, 95% confidence interval 0.01-0.65). Carriers of FLG mutations who have had hand eczema onset in childhood avoid occupational exposure to irritants; the association is most marked with homozygous mutation status combined with atopic dermatitis.
    Contact Dermatitis 06/2013; 69(6). DOI:10.1111/cod.12097 · 3.62 Impact Factor
  • American Journal of Hematology 05/2013; 88(5):E57-E57. · 3.48 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Loss-of-function mutations of the filaggrin (FLG) gene cause an impaired skin barrier and increase the risk of atopic dermatitis. Interestingly, FLG mutations have also been found to be associated with a high risk of peanut allergy. Objective: We investigated the association of FLG mutations with self-reported food allergy, symptoms of oral allergy syndrome (OAS), and alcohol sensitivity. Methods: A total of 3,471 adults from the general population participated in a health examination. Information on food allergies, OAS and alcohol sensitivity was obtained by questionnaire. FLG mutation carriers were defined as having at least one null mutation allele of R501X or 2282del4. Primary lactose intolerance (PLI) was defined as the C/C genotype of the rs4988235 polymorphism. Results: FLG mutations were associated with a higher risk of self-reported allergy to eggs (OR 3.22 and 95% CI 1.46-7.11), milk (OR 2.10 and 95% CI 1.12-3.92), fish (OR 4.54 and 95% CI 1.88-10.96) and wheat (OR 3.59 and 95% CI 1.61-8.02), but not with symptoms of OAS (OR 1.05 and 95% CI 0.73-1.51). Serum-specific IgE was measured in a subsample and confirmed the association between FLG and IgE to milk. A significant gene-by-gene interaction between FLG and PLI was observed in relation to self-reported allergy to milk. Furthermore, FLG mutations were associated with a higher risk of alcohol sensitivity. Conclusions: We found that loss-of-function mutations in the FLG gene were significantly associated with self-reported food allergy and alcohol sensitivity, but not with OAS. These findings, if confirmed, support the idea that skin barrier functions may be involved in the pathogenesis of food allergy.
    International Archives of Allergy and Immunology 03/2013; 161(3):234-242. DOI:10.1159/000345949 · 2.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Vitamin D deficiency is associated with increased cardiovascular disease risk in observational studies. Whether these associations are causal is not clear. Loss-of-function mutations in the filaggrin gene result in up to 10% higher serum vitamin D concentrations, supposedly due to a decreased UV-protection of the keratinocytes. We used a Mendelian randomization approach to estimate the causal effect of vitamin D status on serum lipids, blood pressure, body mass index, waist circumference, and the metabolic syndrome. Three population based studies were included, Monica10 (2,656 individuals aged 40-71 years), Inter99 (6,784 individuals aged 30-60 years), and Health2006 (3,471 individuals aged 18-69 years) conducted in 1993-94, 1999-2001, and 2006-2008, respectively. Participants were genotyped for the two most common filaggrin gene mutations in European descendants R501X and 2282del4, in all three studies and further for the R2447X mutation in the Inter99 and Health2006 studies. Filaggrin genotype was used as instrumental variable for vitamin D status. Baseline measurements of serum 25-hydroxyvitamin D were performed in all three studies. Instrumental variable analyses showed a 23.8% (95% confidence interval, CI 3.0, 48.6) higher HDL cholesterol level and a 30.5% (95% CI: 0.8, 51.3) lower serum level of triglycerides per doubling of vitamin D. These associations were, however, not statistically significant when applying the Bonferroni adjusted significance level. The remaining lipids showed non-significant changes in a favorable direction. Doubling of vitamin D gave a non-significantly lower odds ratio = 0.26 (95% CI: 0.06, 1.17) of the metabolic syndrome. There were no statistically significant causal effects of vitamin D status on blood pressure, body mass index, or waist circumference. Our results support a causal effect of higher vitamin D status on a more favorable lipid profile, although more studies in other populations are needed to confirm our results.
    PLoS ONE 02/2013; 8(2):e57647. DOI:10.1371/journal.pone.0057647 · 3.53 Impact Factor

27 Following View all

44 Followers View all