Mendelian randomisation study of the associations of vitamin B12 and folate genetic risk scores with blood pressure and fasting serum lipid levels in three Danish population-based studies.

BACKGROUND/OBJECTIVES: The aim was to examine the association of genetic risk scores (GRSs) of vitamin B12 and folate-associated variants with blood pressure and lipids. SUBJECTS/METHODS: The study included 12 532 adults from three population-based studies (Inter99, Health2006 and Dan-MONICA10) conducted in Denmark. GRSs were calculated by summarising the number of vitamin B12 and folate increasing alleles. Weighted GRSs were calculated as the sum of weights for each allele corresponding to genetic effects sizes. RESULTS: GRSs for serum vitamin B12 and folate were associated with serum vitamin B12 and folate, respectively. The ß coefficients (95% confidence interval (CI), P-value) for regression of log-transformed serum B12/folate on the weighted GRSs were 0.57 (0.54, 0.61), P<0.001 and 0.85 (0.70, 1.01), P<0.01. No associations were observed between the vitamin B12 GRSs and any of the blood pressure and lipid-related outcomes in the combined analyses. Increasing number of folate increasing alleles was associated with increased high-density lipoprotein (HDL) cholesterol concentrations (ß coefficient (95% CI, P-value) for regression of log-transformed HDL on the weighted GRSs, 0.081 (0.015, 0.148), P=0.017), but not with blood pressure, triglyceride, and low-density lipoprotein and total cholesterol levels. CONCLUSIONS: GRSs were not associated with blood pressure and lipid levels, except for an association between the GRS for folate and HDL cholesterol. Further studies are needed to determine whether a causal association between folate and HDL cholesterol exists.

Serum 25-hydroxyvitamin D and self-reported mental health status in adult Danes.

BACKGROUND/OBJECTIVES: Vitamin D receptors and vitamin D-metabolising enzymes are present in the brain and in the central nervous system at sites responsible for the regulation of emotions and behaviour. This raises the hypothesis that low vitamin D is related to poor mental health. Our aim was to examine the association between serum 25-hydroxyvitamin D (25(OH)D) and the self-reported symptoms and diagnosis of depression and anxiety in the adult general population. SUBJECTS/METHODS: Serum 25(OH)D was measured in three Danish population-based studies, including 5308 adults aged 18-64 years. After 5 years, 2004 participants were re-examined. Symptoms of depression and anxiety were assessed by the Symptom Check List (SCL)-90-R, and self-reported doctor-diagnosed depression and anxiety was recorded by using a questionnaire. RESULTS: Serum 25(OH)D was not associated with SCL average scores for depression and anxiety when analysed by quantile median regression adjusted for sex, age and other potential confounders. The ß-coefficient and 95% confidence interval (CI) per 10 nmol/l serum 25(OH)D were 0.00 (-0.00 to 0.01) and P=0.23 for depression and -0.00 (-0.01 to 0.00) and P=0.19 for anxiety. Furthermore, no evidence of an association was observed with longitudinal changes (combining depression and anxiety score: ß (95% CI)=0.00 (-0.00 to 0.00), P=0.90), with scores >90 percentiles (odds ratio (OR) (95% CI)=1.02 (0.98-1.07), P=0.32), or with self-reported history (OR (95% CI)=1.02 (0.97-1.07), P=0.47) or incidence (OR (95% CI)=1.02 (0.92-1.12), P=0.77) of doctor-diagnosed depression and/or anxiety. CONCLUSIONS: Our results suggest that low serum 25(OH)D is not associated with self-reported symptoms/diagnosis of depression and anxiety.

The Danish urban-rural gradient of allergic sensitization and disease in adults.

BACKGROUND: The reported prevalence of allergic sensitization among children is lower in rural areas than in urban areas of the world. The aim was to investigate the urban-rural differences of allergic sensitization to inhalant allergens in adults depending on childhood exposure living in an industrialized country as Denmark. METHODS: A total of 1236 male participants of 30-40 years of age recruited from two epidemiological studies were divided into four groups with regard to place of upbringing; city, town, rural area and farm. Allergic sensitization was assessed by skin prick tests (SPTs) to 10 inhalant allergens and measurements of serum specific IgE (sIgE) to four inhalant allergens (grass, birch, cat and house dust mite). RESULTS: The prevalence of allergic sensitization to inhalant allergens decreased with decreasing degree of urbanized childhood. The risk of being sensitized to one or more allergens also decreased with decreasing degree of urbanized upbringing measured by sIgE to 4 common allergens as odds ratio with 95% confidence intervals with city as reference; town 0.60 (0.39-0.92), rural area 0.34 (0.22-0.52) and farm 0.31 (0.21-0.46). Furthermore, it was measured by SPT to 10 common allergens; town 0.52 (0.33-0.84), rural area 0.34 (0.21-0.53) and farm 0.29 (0.19-0.45). This urban-rural association was also seen for the risk of sensitization to specific allergens, rhinitis and allergic asthma. CONCLUSION: This is the first study to show an urban-rural gradient of overall allergic sensitization and specific allergen sensitization in adults depending on their childhood exposure. In this highly homogenous western population, exposure to a less urbanized childhood was associated with lower risk of allergic sensitization and disease as an adult.

17q21 gene variation is not associated with asthma in adulthood.

BACKGROUND: 17q21 gene variants are the strongest known genetic determinants for childhood asthma and have been reported to interact with environmental tobacco smoke exposure in childhood. It remains unclear whether individuals with 17q21 risk variants have increased risk of asthma or reduced lung function in adulthood. The aim was to examine the association between the 17q21 region and current adult asthma and lung function, and interaction with active smoking. METHODS: We investigated the single nucleotide polymorphism rs7216389 at the 17q21 locus in 3471 adults from the Health2006 cross-sectional study and in 7008 adults from The British 1958 Birth Cohort and examined the association with current asthma, spirometry measures, and related atopic traits. Analyses were performed for interaction with active smoking. RESULTS: We found no association between rs7216389[T] and asthma when meta-analyzed (OR = 1.02 [0.92-1.13], P = 0.81). The risk variant was associated with reduced FEV1 as compared to normal FEV1 (OR = 1.10 [1.01-1.12], P = 0.033) and with allergic sensitization (OR = 1.10 [1.03-1.17], P = 0.003). Individuals with rs7216389 risk variants smoked as frequently as individuals without risk variants, and there was no evidence that smoking modified the association between rs7216389 and asthma. CONCLUSION: Our study suggests that the 17q21 rs7216389 locus variant does not substantially influence asthma risk in adulthood or susceptibility to detrimental effects of active smoking. This contrasts the findings in children and suggests that this locus is associated with a childhood-specific asthma endotype.

The association of serum 25-OH vitamin D with atopy, asthma, and lung function in a prospective study of Danish adults.

BACKGROUND: Besides the important skeletal functions, it has been suggested that vitamin D is involved in the pathogenesis of allergy and asthma and related to lung function. However, previous studies are inconclusive. OBJECTIVE: The purpose of this study was to investigate associations of serum levels of 25-hydroxy vitamin D (25(OH)D) with atopy, asthma, and lung function in a prospective study of Danish adults. METHODS: This study included 4999 adults aged 30-60 years in 1999-2001. Three thousand and thirty-two of those included at baseline also participated at a follow-up examination 5 years later, and 3727 answered a 10-year follow-up questionnaire. Serum levels of (25(OH)D) were measured by high-performance liquid chromatography (HPLC) at baseline. No information on use of vitamin D supplements was available. Specific IgE against four common antigens was measured. Information about doctor-diagnosed asthma was obtained from questionnaires, and lung function (FEV1 and forced vital capacity) was measured by spirometry. RESULTS: We found no significant associations of 25(OH)D with atopy and doctor-diagnosed asthma. However, we found that low levels of 25(OH)D were associated with lower FEV1 percentage predicted (FEV1%pred) in the cross-sectional analyses. The odds ratio (OR) of FEV1%pred < 80% among participants in the highest quartile of 25(OH)D compared with those in the lowest was 0.66 (95% confidence interval (CI): 0.49-0.74). In contrast, prospective analyses indicated an association between high levels of 25(OH)D at baseline and adverse changes in lung function. OR (95%CI) of incident FEV1%pred < 80% was 1.73 (1.06-2.82) in the highest quartile of 25(OH)D compared with the lowest. CONCLUSIONS AND CLINICAL RELEVANCE: Our data indicates that 25(OH)D levels do not influence the development of asthma and allergy among adults. Further, the results did not consistently support that 25(OH)D levels associate with lung function. Randomized controlled trials are needed to further address this issue.

Atopy and cause-specific mortality.

BACKGROUND: Atopy is the familial or personal propensity to develop immunoglobulin E (IgE) antibodies against common environmental allergens and is associated with high risk of allergic disease. It has been proposed that atopy may have effects on risk of cardiovascular disease and cancer. OBJECTIVES: We investigated the association of atopy with all-cause and cause-specific mortality. METHODS: We included a total of 14 849 individuals from five Danish population-based cohorts with measurements of atopy defined as serum-specific IgE positivity against inhalant allergens. Participants were followed by linkage to the Danish Registry of Causes of Death to obtain information on mortality status and cause of death (median follow-up time 11.3 years). The relative mortality risk was estimated by Cox regression and expressed as hazard ratios, HRs (95% confidence intervals, CIs). RESULTS: A total of 1776 person died during follow-up. The mortality risk for atopics vs. non-atopics was: for all-cause mortality (HR = 1.03, 95% CI: 0.90, 1.17); neoplasms (HR = 0.86, 95% CI: 0.69, 1.06); endocrine, nutritional and metabolic disorders (HR = 1.48, 95% CI: 0.71, 3.08); mental and behavioural disorders (HR = 2.26, 95% CI: 1.18, 4.30); diseases of the nervous system (HR = 1.36, 95% CI: 0.65, 2.87); diseases of the circulatory system (HR = 1.00, 95% CI: 0.78, 1.29); diseases of the respiratory system (HR = 0.94, 95% CI: 0.55, 1.60); and diseases of the digestive system (HR = 1.75, 95% CI: 1.03, 2.98). CONCLUSIONS & CLINICAL RELEVANCE: We found no statistically significant association between atopy and all-cause mortality. However, atopy was associated with a significantly higher risk of dying from mental and behavioural disorders and gastrointestinal diseases, particularly liver diseases, and a lower risk of dying from breast cancer, but these associations were not statistically significant when applying the Bonferroni adjusted significance level. Further studies are needed to confirm our findings.

The association of the 'additional height index' with atopic diseases, non-atopic asthma, ischaemic heart disease and mortality: a population-based study.

OBJECTIVE: Intrauterine growth has been associated with atopic conditions. Growth and adult height have been associated with cardiovascular disease, cancers and mortality but are highly genetic traits. The objectives of the study were as follows: first, to define a height measure indicating an individual's height below or above that which could be expected based on parental height (genetic inheritance) and growth charts. It was named 'the additional height index' (AHI), defined as (attained-expected) height; second, to investigate possible associations of AHI with atopic versus non-atopic health outcomes and with ischaemic heart disease (IHD) and IHD mortality. DESIGN: General population-based study. SETTING: Research centre. PARTICIPANTS: A random sample of 2656 men and women living in greater Copenhagen took part in the MONICA10 study (the Danish monitoring trends and determinants of cardiovascular disease). In total, 1900 participants with information of parental height were selected. OUTCOME MEASURES: Atopic sensitisation (serum IgE), questionnaire information of atopic dermatitis, rhinoconjunctivitis, asthma or wheezing, and registry-based diagnoses of IHD/IHD mortality from National Registries. RESULTS: Increasing levels of AHI were inversely associated with non-atopic asthma, non-atopic wheezing, IHD and IHD mortality (IHD-all). For one SD increase of AHI, the OR or HR with CI in adjusted analyses was non-atopic asthma OR=0.52 (0.36 to 0.74), non-atopic wheezing OR=0.67 (0.51 to 0.89), and IHD-all HR=0.89 (0.78 to 1.01). The level of AHI was higher among individuals with atopic dermatitis, allergic rhinoconjunctivitis and atopic sensitisation (all p values <0.001) compared with individuals without those conditions; however, the associations were not confirmed in adjusted analyses. CONCLUSIONS: Individuals with childhood conditions that led them to attain tallness higher than expected from their parents' height may be at lower risk of non-atopic asthma/wheeze and IHD/IHD mortality but possibly at higher risk of atopic conditions. The measure of tallness below or above the expected height could be a sensitive alternative to normal height in epidemiological analyses.

Filaggrin loss-of-function mutations and incident cancer: a population-based study.

BACKGROUND: Loss-of-function mutations in the filaggrin gene (FLG) could have opposing effects on cancer risk, as mutations are associated with both 10% higher serum vitamin D levels, which may protect against cancer, and with impaired skin barrier function, which may lead to higher cancer susceptibility. OBJECTIVES: To investigate the association of the FLG genotype and cancer types in four population-based cohorts. METHODS: A total of 13,376 individuals were genotyped for FLG mutations. Information on cancer was obtained from the Danish Cancer Registry. Persons with a history of cancer at baseline were excluded from prospective analyses. RESULTS: There were 1339 incident cancers (median follow-up 11·4 years). The hazard ratios (HRs) and 95% confidence intervals (CIs) for FLG mutation carriers vs. wild types were: for any cancer (HR 0·95, 95% CI 0·78-1·16), any cancer excluding nonmelanoma 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), bronchus and lung cancer (HR 1·34, 95% CI 0·77-2·33), breast cancer (HR 0·58, 95% CI 0·30-1·14), uterine cancer (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). Among participants aged over 60 years at baseline, we found statistically significant lower risks of all cancers and NMSC among FLG mutation carriers. CONCLUSIONS: The only significant associations between FLG loss-of-function mutations and cancer were in subgroup analyses.

Investigating the causal effect of vitamin D on serum adiponectin using a Mendelian randomization approach.

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.

The relationship of serum triglycerides, serum HDL, and obesity to the risk of wheezing in 85,555 adults.

BACKGROUND: Asthma has been linked to obesity and the presence of the metabolic syndrome. OBJECTIVE: To explore which components of the metabolic syndrome that were associated with wheezing, a main symptom of asthma. Further, to explore whether these associations were different in individuals with and without rhinitis symptoms. METHODS: We used data from the Ibermutuamur Cardiovascular Risk Assessment Plan (ICARIA) including 85,555 Spanish workers (median age = 34, range = 16-75 years) with assessments of self reported wheezing and rhinitis symptoms. Fasting blood samples were analysed for serum triglyceride (s-TG), HDL (s-HDL) and glucose; blood pressure, waist circumference (WC) and body mass index (BMI) were measured. RESULTS: In mutually adjusted analyses including all components of the metabolic syndrome and possible confounders, elevated WC (or BMI), elevated s-TG and low s-HDL were significantly associated with wheezing. Odds ratio (OR) with confidence interval (CI) were: elevated WC = 1.54 (1.46-1.62), elevated s-TG = 1.24 (1.18-1.30), low s-HDL = 1.17 (1.12-1.22). These associations were stronger in individuals without than in those with rhinitis symptoms, OR's (CI's) were WC = without rhinitis 1.70 (1.57-1.85) vs. with rhinitis 1.47 (1.37-1.58). Elevated s-TG = without rhinitis 1.36 (1.26-1.46) vs. with rhinitis 1.21 (1.13-1.29). Low s-HDL = without rhinitis 1.24 (1.15-1.34) vs. with rhinitis 1.11 (1.04-1.18). CONCLUSIONS: High s-TG and low s-HDL were associated with wheezing after adjustment for adiposity. This may substantiate elevated s-TG and lowered s-HDL as markers or inducers of inflammation associated disease. The study supports the notion that these biochemical markers have differential effects on different types of wheezing.

Serum 25(OH)D and incident type 2 diabetes: a cohort study.

BACKGROUND/OBJECTIVES: Mild to moderate vitamin D insufficiency has been proposed as a risk factor for several common chronic diseases including type 2 diabetes. This study aimed to examine the association between serum 25-hydroxy vitamin D (25(OH)D) and incident diabetes. SUBJECTS/METHODS: The MONICA10 cohort consists of 2656 participants (men and women aged 41-71 years) who participated in a 10-year follow-up examination during 1993-1994 as part of the MONICA 1 population survey. A total of 2571 participants free of diabetes at baseline and with successful measurement of serum 25(OH)D were included in the current study. The Danish National Diabetes register enabled identification of 288 cases of incident diabetes during follow-up (median: 16.4 years). Data were analysed by Cox proportional hazard models and associations were expressed as hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: Serum 25(OH)D was inversely associated with incident diabetes adjusted for potential confounders (HR per 25 nmol/l=0.83; 95% CI: 0.72-0.95; P=0.009). A statistically significant interaction was observed between 25(OH)D and waist circumference (WC) (P(interaction)=0.042) suggesting an association in persons with a high WC (HR (95%CI) per 25 nmol/l=0.74 (0.63-0.88), 218 incident cases) and not in persons with a normal WC (HR (95%CI) per 25 nmol/l=0.98 (0.78-1.24), 70 incident cases). CONCLUSIONS: Low serum 25(OH)D was associated independently with incident diabetes. The inverse association was only found in overweight-obese and not in normal weight individuals, suggesting that obesity may modify the effect of vitamin D status on the risk of diabetes.

Atopy, asthma, and lung function in relation to folate and vitamin B(12) in adults.

BACKGROUND: Recent studies suggested low serum folate and impaired folate metabolism as potential risk factors for development of asthma and atopic disease, but the results are inconsistent. The aim of this study was to investigate the relations of markers of folate and vitamin B12 (B12) deficiency with different phenotypes of asthma and atopy. METHODS: A random sample of 6784 persons from a general population aged 30-60 years participated in a health examination in 1999-2001, and 4516 (66.6%) of those also participated in a follow-up examination 5 years later. The examinations included spirometry, measurements of serum folate and B12, specific IgE to inhalant allergens, total IgE, and genotyping of the MTHFR-C677T polymorphism - a genetic marker of impaired folate metabolism. Information about dietary intake of folate and B12, asthma diagnosis, and airway symptoms was obtained by questionnaires. RESULTS: Low serum folate levels and the TT genotype of the MTHFR-C677T polymorphism were associated with increased prevalence of self-reported doctor-diagnosed asthma [odds ratio (OR) 1.37, 95% confidence interval (CI) 1.05-1.79 and OR 1.52; 95% CI 1.12-2.06, respectively] and attacks of shortness of breath (OR 1.43, 95% CI 1.14-1.79 and OR 1.47; 95% CI: 1.14-1.91, respectively). We found no significant associations with lung function or atopic outcomes. Serum levels of B12 and dietary intake of folate and B12 were not associated with asthma or atopy. CONCLUSIONS: We found that two objective markers of folate deficiency were associated with self-reported doctor-diagnosed asthma and attacks of shortness of breath, but not with lung function or atopy.

Genetic determinants of both ethanol and acetaldehyde metabolism influence alcohol hypersensitivity and drinking behaviour among Scandinavians.

BACKGROUND: Although hypersensitivity reactions following intake of alcoholic drinks are common in Caucasians, the underlying mechanisms and clinical significance are not known. In contrast, in Asians, alcohol-induced asthma and flushing have been shown to be because of a single nucleotide polymorphism (SNP), the acetaldehyde dehydrogenase 2 (ALDH2) 487lys, causing decreased acetaldehyde (the metabolite of ethanol) metabolism and high levels of histamine. However, the ALDH2 487lys is absent in Caucasians. OBJECTIVES: To investigate the genetic determinants of self-reported alcohol-induced hypersensitivity reactions in Caucasians. METHODS: The study included two population-based studies of 1216 and 6784 adults living in Copenhagen. Assessment of alcohol consumption and hypersensitivity reactions (in a subgroup) was performed by a questionnaire and was related to common SNPs of genes encoding alcohol dehydrogenases (ADHs) and ALDHs. RESULTS: In both populations, alcohol drinkers with a genetically determined fast metabolism of ethanol (the A allele of the ADH1b rs1229984) had an increased risk of alcohol-induced hypersensitivity reactions (odds ratio AA/AG vs. GG in combined populations: 1.82, 95% CI 1.04-3.17). In both populations, a common SNP encoding ALDH1b1 (rs2228093) was found to be significantly associated with alcohol-induced hypersensitivity (odds ratio TT vs. CC in combined populations: 2.53, 95% CI 1.31-4.90). CONCLUSIONS: Our data support that alcohol sensitivity in Caucasians is genetically determined and suggest that a histamine-releasing effect of acetaldehyde represents a plausible biological mechanism. Furthermore, we present the first report of a clinically significant SNP within the acetaldehyde-metabolizing system in a Caucasian population.

Incidence and remission of specific IgE aeroallergen sensitization from age of 40 to 60 years, and association with alcohol consumption.

BACKGROUND: Data on incidence and long-term persistence of IgE aeroallergen sensitization in older adults are limited. Alcohol consumption is a strong immune-modulator with a significant impact on the IgE response. OBJECTIVES: We aimed to assess the incidence and remission of aeroallergen sensitization from the age of 40 to 60 years. Furthermore, we examined the relationship of alcohol consumption to the prevalence and incidence of aeroallergen sensitization. METHODS: In 1976-1977, a total of 1,200 people born in 1936 and randomly selected from the general population were invited for a health examination (1,052 were examined). At 60 years, they were invited for a re-examination (695 were examined). Stored serum samples from both examinations were analyzed consecutively for serum-specific IgE to aeroallergens by using a qualitative multi-allergen immunoassay. RESULTS: We observed a total of 32 (7.1% of those not sensitized at 40 years) incident cases and 35 (41.1% of those sensitized at 40 years) remittent cases of aeroallergen sensitization over this 20 year period. Persistent as well as incident sensitization was significantly associated with self-reported atopic disease at 60 years. Alcohol consumption (>14 drinks per week) at 40 years was significantly associated with a higher prevalence of sensitization at 40 years, but not with the incidence of sensitization. CONCLUSIONS: In older adults, aeroallergen sensitization as reflected by serum-specific IgE positivity to aeroallergens is a dynamic process. Both persistent and incident sensitization was associated with atopic disease. Further studies are needed to clarify the influence of alcohol on the allergen-specific IgE response.

Changes in lifestyle, biological risk factors and total homocysteine in relation to MTHFR C677T genotype: a 5-year follow-up study.

BACKGROUND/OBJECTIVES: Total homocysteine (tHcy) has been associated with increased risk of several diseases in the general population. It is not clear whether these associations are causal. A less healthy lifestyle as well as a less favorable biological risk factor profile have been related to increased tHcy in cross-sectional studies. In addition, the methylenetetrahydrofolate reductase (MTHFR) C677T gene variant is an important determinant of elevated tHcy. The main objective of the study was to examine the effect of changes in biological risk factors and lifestyle on tHcy in relation to MTHFR C677T genotype. SUBJECTS/METHODS: The study is a population-based study including 1805 men and women aged 30-60 years participating in a health examination at baseline (1999-2001) and at a 5-year follow-up examination. RESULTS: Changes in tHcy were not associated with changes in dietary habits, physical activity, smoking status, coffee, tea, total alcohol or wine consumption. An inverse relationship was observed between changes in tHcy and changes in the intake of beer in TT individuals but not in CC/CT individuals (P (interaction)=0.01). In addition, changes in tHcy were positively associated with changes in several biological risk factors, such as waist circumference, diastolic blood pressure, total cholesterol and LDL cholesterol (P<0.01). The association between waist circumference and MTHFR genotype seemed stronger in TT individuals than in CC/CT individuals (P (interaction)=0.03). CONCLUSIONS: tHcy was not influenced by lifestyle changes except for the inverse association between beer consumption and tHcy observed in TT individuals. This suggests that tHcy is not a mediator in the causal pathway between lifestyle and lifestyle-related diseases such as cardiovascular disease in accordance with results of recent randomized trials. However, tHcy was related to changes in several biological risk factors, suggesting that tHcy may be a good predictor or marker of disease.

Insulin resistance as a predictor of incident asthma-like symptoms in adults.

BACKGROUND: There is accumulating evidence that obesity is associated with an increased risk of asthma. It has been hypothesized that insulin resistance may be involved in obesity-induced asthma, but till date there is no prospective data on this issue. OBJECTIVE: To investigate the association of obesity and insulin resistance with the incidence of asthma-like symptoms in adults. METHODS: Out of a random sample of 12 934 persons from a general population, 6784 (52.5%) were included and participated in a health examination in 1999-2001. After 5 years they were re-invited and 4516 (66.6%) participated at follow-up. At baseline three obesity measures were considered: body mass index, waist circumference, and waist-to-hip ratio. In addition, fasting glucose and insulin were measured for determination of insulin resistance. Information on asthma-like symptoms at baseline and follow-up were obtained by questionnaires. A total of 3441 participants defined as non-asthmatic at baseline and with complete information on all the considered variables were included in the analyses. Data were controlled for confounding by sex, age, social status, and smoking. RESULTS: All obesity measures were associated with incident wheezing and asthma-like symptoms. In addition, insulin resistance was associated with incident wheezing [odds ratio (OR) 1.87, 95% confidence interval (CI) 1.38-2.54] and asthma-like symptoms (OR 1.61, 95% CI 1.23-2.10). The effect of insulin resistance was stronger than that of obesity and was independent of sex. CONCLUSION: We found that insulin resistance was associated with an increased risk of developing asthma-like symptoms. This finding supports the hypothesis that obesity and asthma may be linked through inflammatory pathways also involved in insulin resistance.

Association of obesity and insulin resistance with asthma and aeroallergen sensitization.

BACKGROUND: It has been hypothesized that obesity and insulin resistance may play a role in the development of asthma and allergy. The aim of the study was to examine the association of obesity and insulin resistance with asthma and aeroallergen sensitization. METHODS: Cross-sectional population-based study of 3609 Danish men and women aged 30-60 years. Aeroallergen sensitization was defined as positive levels of specific IgE against a panel of inhalant allergens. Asthma was defined as self-reported physician diagnosed asthma. Allergic asthma was defined as the presence of both asthma and aeroallergen sensitization. The homeostasis model assessment of insulin resistance was used to estimate the degree of insulin resistance. Body mass index, waist-to-hip ratio, and waist circumference were used as measures of obesity. Data were analyzed by multiple logistic regression analyses. RESULTS: Obesity was associated with increased risk of aeroallergen sensitization as well as allergic and nonallergic asthma. Insulin resistance was asssociated with aeroallergen sensitization and allergic asthma, but not nonallergic asthma. The associations of obesity with aeroallegen sensitization and allergic asthma became nonsignificant after adjustment for insulin resistance, whereas the association of obesity with nonallergic asthma was unaffected. No sex-differences were observed. CONCLUSION: Obesity may be related to an increased risk of aeroallergen sensitization and allergic asthma through mechanisms also involved in the development of insulin resistance.

Temporal trends of aeroallergen sensitization over twenty-five years.

BACKGROUND: Little is known about time trends of allergic respiratory disease in adults, in particular in older adults. Furthermore, few trend studies have used objective measurements of IgE sensitization against inhalant allergens. OBJECTIVES: To investigate time trends of aeroallergen sensitization in adults over a 25-year period. METHODS: The study includes a total of 7820 persons, aged 30, 40, 50, and 60 years, who participated in three repeated cross-sectional studies of the general population of Copenhagen, Denmark, in 1976-1977, 1982-1984, and 1999-2001, respectively. Respiratory allergy was assessed by determination of specific IgE aeroallergen sensitization in stored serum samples. RESULTS: Over this 25-year period, a marked and statistically significant increase in the prevalence of aeroallergen sensitization had occurred. This increase was seen in all age-groups challenging the notion that the allergy epidemic only affects generations born 1960 onwards. For example, in 40-year-olds the prevalence (with 95% confidence intervals) of aeroallergen sensitization was 14.9% (12.7-17.1), 19.7% (17.1-22.3), and 27.6% (25.1-30.1) in 1976-1977, 1982-1984, and 1999-2001, respectively. CONCLUSIONS: Our results support that the allergy epidemic has spread to older adults resulting in a continuing increase in the overall prevalence of aeroallergen sensitization and an increase in the mean age of allergic patients.

Association between alcohol consumption and aeroallergen sensitization in Danish adults.

BACKGROUND: It has been proposed that alcohol consumption may be one of the lifestyle factors associated with a westernized, urban, and affluent lifestyle contributing to the rise in atopic disease. OBJECTIVE: The aim was to investigate the association between alcohol consumption and atopy (aeroallergen sensitization). METHODS: In 1982, a population-based cross-sectional study of 3608 Danes (79% of the invited), aged 30, 40, 50, and 60 years, was carried out. Information on alcohol consumption was obtained by a questionnaire. Aeroallergen sensitization was defined as a positive test for the detection of specific IgE against a panel of 19 common inhalant allergens in stored serum samples. A total of 3317 subjects with complete information on all variables were included in the analyses. RESULTS: We found a statistically significant association between alcohol consumption and aeroallergen sensitization (independent of the type of alcoholic drink consumed). This association appeared to relate only to those who consumed more than 8 drinks/week. After adjustment for confounders this association was only statistically significant for those who consumed 15-21 drinks/week (adjusted odds ratio 1.8, 95% confidence interval 1.2-2.8). CONCLUSION: In this adult general population, self-reported alcohol consumption was positively associated with aeroallergen sensitization.