National Allergy Research Centre, Department of Dermato-Allergology, Copenhagen University Hospital Gentofte, University of Copenhagen, Niels Andersens Vej 65, 2900 Hellerup, Denmark. firstname.lastname@example.org
It was recently shown that filaggrin gene (FLG) null mutations are positively associated with nickel sensitization. We have hypothesized that histidine-rich filaggrin proteins in the epidermis chelate nickel ions and prevent their skin penetration and exposure to Langerhans cells. Furthermore, we have proposed that the low degree of genetic predisposition to nickel sensitization found by a Danish twin study was explained by a high prevalence of ear piercing among participants resulting in 'bypassing' of the filaggrin proteins.
To investigate the association between FLG null mutations and (nickel) contact sensitization.
A random sample of 3335 adults from the general population in Denmark was patch tested and genotyped for R501X and 2282del4 in the FLG gene.
The combined carrier frequency of FLG null mutations was 8·1%. Nickel, fragrance and contact sensitization to at least one allergen were not associated with FLG null mutations. A crude analysis on women who did not have ear piercings revealed a positive association between FLG null mutations and nickel sensitization [8·3% vs. 2·4%; odds ratio (OR) 3·71, 95% confidence interval (CI) 0·73-18·96] as well as between FLG null mutations and allergic nickel dermatitis (8·3% vs. 1·3%; OR 6·75, 95% CI 1·17-38·91). FLG mutation status and atopic dermatitis were positively associated with neomycin or ethylenediamine sensitization.
This study suggests that FLG null mutations may be a risk factor for the development of nickel sensitization. However, ear piercing was a much stronger risk factor in our general population and we could therefore identify a positive association only in women without ear piercings. Contact sensitization to specific chemicals is related to treatment exposure.
The prevalence of atopic disorders has increased in recent years. The pathogenesis is complex with genetic and environmental risk factors. Filaggrin loss-of-function mutations are common and associated with atopic disorders. We investigated whether the prevalence of filaggrin mutations increased in different birth cohorts in adults from the general population in Denmark.
Cross-sectional questionnaire and filaggrin gene mutation (R501X and 2282del4) data from 3335 18- to 69-year-old adults were available for analyses.
The effect of filaggrin mutations on the prevalence of atopic diseases, albeit not statistically significant, depended mostly on birth year for atopic dermatitis (AD). A nonsignificant increase in the prevalence of filaggrin mutations was noted across birth year groups reporting AD, with 12.9% in adults born in 1936-1949 and 19.0% born in 1976-1988.
If confirmed in other populations, the observed increase suggests that mutation carriers have been more susceptible to environmental changes accentuating the rise in AD prevalence.
In order to survey trends in food habits the Danish Nutrition Council initiated two food frequency surveys, comprising ten nutritionally important foods, in 1995 and in 1998. Participants were men and women, 15-90 yrs, from similar population samples (n = 1007 in 1995, 1024 in 1998). Participation rate was 62% in 1995 and 63% in 1998. Data were collected by telephone interview. For six of the ten foods significant changes in consumption frequencies were observed: salad/raw vegetables, rice/pasta and fish were consumed more frequently in 1998, whereas consumption of meat, potatoes and fresh fruit had become less frequent. Average frequencies differed by 4-13%. In 1998 low-fat milk had become more common, whereas whole milk was now less common. More subjects now skipped fat spreads on their bread, but more chose spreads containing butterfat. Some, but not all, of the observed changes point in the right direction compared to recommendations. The results demonstrate that food habits are currently in a dynamic process.
Food costs for 30 children under dietary treatment for familial hypercholesterolaemia were compared with those of 105 other Danish children. The daily intake of macronutrients and the daily cost of the diet for each child were calculated from dietary intakes and average prices of 365 different food items. The mean +/- SE percentages of energy (E%) from fat in the diet of children with and without known familial hypercholesterolaemia were 23.6 +/- 0.8 E+ and 34.5 +/- 0.5 E%, respectively (P
BACKGROUND: Studies of long-term intake of industrially produced trans fatty acids (TFA) and n-3 polyunsaturated fatty acids (PUFA) suggest opposite effects on cardiovascular disease risk. Common mechanisms of action are probable. OBJECTIVE: To examine the effects on cardiovascular risk markers of dietary enrichment with TFA or n-3 PUFA. DESIGN: Randomized, double-blind, parallel intervention trial. SETTING: Department of Human Nutrition, The Royal Veterinary and Agricultural University. SUBJECTS: In all, 87 healthy males included, 79 completed. INTERVENTION: Subjects were randomly assigned to 8 weeks of a daily intake of 33 g of experimental fats from either partially hydrogenated soy oil containing 20 g of TFA, 12 g of fish oil with approximately 4 g of n-3 PUFA and 21 g of control fat, or 33 g of control fat. The experimental fats were incorporated into bakery products. Plasma lipids, blood pressure, heart rate variability (HRV), arterial dilatory capacity, compliance, and distensibility were recorded before and after intervention and at follow-up 12 weeks after the intervention. RESULTS: High-density lipoprotein cholesterol (HDL-C) decreased in the TFA group and triglycerides and mean arterial blood pressure decreased in the n-3 PUFA group compared to the control group. HRV, arterial dilatory capacity, compliance, and distensibility were unchanged. CONCLUSION: The results indicate that the association between coronary heart disease risk and intake of TFA and n-3 PUFA relates only modestly to changes in traditional risk markers. SPONSORSHIP: Danish Medical Research Council (Grant no. 22-01-0390), Center of Advanced Food Research (Copenhagen, Denmark) (Grant no. KVL-R-2001-107), the Danish Heart Association (Grant no. 99-2-3-45-22748), Novozymes (Bagsvaerd, Denmark), Aarhus Olie (Aarhus, Denmark), and from private sources. The experimental fats were provided by Pronova Biocare (Aalesund, Norway) and Aarhus Olie (Aarhus, Denmark).
Psoriasis vulgaris could be associated with the filaggrin null genotype since certain known susceptibility loci for psoriasis are shared with susceptibility loci for atopic dermatitis. Furthermore, filaggrin expression is lowered in psoriatic skin lesions but normally expressed in uninvolved skin. So far five relatively small patient-based case-control studies have rejected a possible association between psoriasis and the two most prevalent filaggrin null mutations, 2282del4 and R501X.
To reinvestigate a possible association between psoriasis and filaggrin null mutation status by using cross-sectional general population questionnaire data. Also, to perform a meta-analysis including published studies that investigated the relation between filaggrin gene mutations R501X and 2282del4, respectively, and psoriasis vulgaris.
Between June 2006 and May 2008, a cross-sectional study was performed in the general population in Copenhagen. A random sample of 7931 subjects aged 18-69 years was invited to participate in a general health examination including a questionnaire and 3471 (43.7%) participated. A total of 3335 (96.1%) individuals were filaggrin genotyped for the 2282del4 and R501X mutations. A meta-analysis was undertaken to investigate the relation between filaggrin gene mutations and psoriasis vulgaris.
The prevalence of self-reported psoriasis was 6.7% among the 3240 respondents. The prevalence of the R501X and 2282del4 filaggrin null genotypes was 9.3% in subjects who reported psoriasis and 8.0% in subjects who did not report psoriasis (OR = 1.28; 95% CI = 0.74-1.89; P = 0.78). The meta-analysis found no association between the filaggrin null genotypes R501X and 2282del4 and psoriasis (OR = 1.04; 95% CI = 0.81-1.35).
Psoriasis was not associated with the R501X and 2282del4 filaggrin null genotypes in a general population study and in a meta-analysis on published studies.
Hand eczema is prevalent in the general population. It remains unclear whether or not filaggrin gene (FLG) null mutations increase the overall risk of hand eczema or only increase the risk of hand eczema in subjects with atopic dermatitis.
To investigate the association between FLG null mutations and hand eczema.
A random sample of 3335 adults from the general population in Denmark was patch tested, FLG genotyped for R501X and 2282del4 null mutations and questioned about hand eczema.
Participants with combined presence of atopic dermatitis and FLG null mutation status had a significantly higher prevalence of hand eczema, an earlier onset of hand eczema and a higher persistence of hand eczema compared with subjects with normal FLG status and absence of atopic dermatitis. Logistic regression analyses revealed positive associations between hand eczema within the past 12 months and FLG null mutation status in participants with a history of atopic dermatitis [odds ratio (OR) 2.98; 95% confidence interval (CI) 1.27-7.01], but not in subjects without atopic dermatitis (OR 0.82; 95% CI 0.41-1.67).
FLG null mutations were significantly associated with hand eczema (
Elevated plasma levels of bilirubin, an endogenous antioxidant, have been associated with reduced risk of ischaemic heart disease (IHD) and myocardial infarction (MI). Whether this is a causal relationship remains unclear.
We tested the hypothesis that elevated plasma bilirubin is causally related to decreased risk of IHD and MI.
We used a Mendelian randomization approach and three independent studies from Copenhagen, Denmark. We measured bilirubin in 43 708 white individuals from the general population, and genotyped rs6742078 G>T in the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene in 67 068 individuals, of whom 11 686 had IHD.
Third versus first tertile of baseline bilirubin levels was associated with 134% increased bilirubin levels, with sex- and age-adjusted hazard ratios (HRs) of 0.86 [95% confidence interval (CI), 0.76-0.98; P = 0.02] for IHD and 0.81 (95% CI, 0.66-0.99; P = 0.04) for MI, but with corresponding multifactorially adjusted HRs of 0.93 (95% CI, 0.82-1.06; P = 0.29) and 0.90 (95% CI, 0.73-1.12; P = 0.35). UGT1A1 rs6742078 TT versus GG genotype was associated with 95% increased bilirubin levels (P