Common filaggrin gene mutations and risk of cervical cancer.

BACKGROUND: As carriers of filaggrin gene (FLG) mutations may have a compromised cervical mucosal barrier against human papillomavirus infection, our primary objective was to study their risk of cervical cancer. METHODS: We genotyped 586 cervical cancer patients for the two most common FLG mutations, R501X and 2282del4, using blood from the Copenhagen Hospital Biobank, Denmark. Controls (n = 8050) were genotyped in previous population-based studies. Information on cervical cancer, mortality and emigration were obtained from national registers. Odds ratios (OR) were estimated by logistic regression with adjustment for age at blood sampling, and weighted by the genotype-specific inverse probability of death between diagnosis and sampling. Hazard ratios (HR) were estimated by Cox regression with time since diagnosis as underlying time, and with adjustment for age at diagnosis and stratification by cancer stage. RESULTS: The primary results showed that FLG mutations were not associated with the risk of cervical cancer (6.3% of cases and 7.7% of controls were carriers; OR adjusted 0.81, 95% CI 0.57-1.14; OR adjusted+ weighted 0.96, 95% CI 0.58-1.57). Among cases, FLG mutations increased mortality due to cervical cancer (HR 4.55, 95% CI 1.70-12.2), however, the association was reduced after stratification by cancer stage (HR 2.53, 95% CI 0.84-7.59). CONCLUSION: Carriage of FLG mutations was not associated with the risk of cervical cancer.

Vitamin D status and changes in cardiovascular risk factors: a prospective study of a general population.

OBJECTIVES: A low vitamin D level has been associated with increased cardiovascular disease risk but possible mechanisms remain unclear. We investigated the association between vitamin D levels and 5-year changes in blood pressure, lipid profile and incidence of the metabolic syndrome, hypertension and hypercholesterolemia. METHODS: A random sample of 6,784 individuals aged 30-60 years from a general population was investigated in the Inter99 study in 1999-2001. Vitamin D (serum 25-hydroxyvitamin D) was measured at baseline by high-performance liquid chromatography, and 4,330 individuals participated at the 5-year follow-up and were included in the present study. RESULTS: The median baseline vitamin D concentration was 48.0 nmol/l. In multivariable linear regression analyses, a 10 nmol/l higher baseline level of vitamin D was associated with a decrease in triglycerides and very low density lipoprotein cholesterol by 0.52 (p = 0.03) and 0.66% (p = 0.005), respectively. In multivariable logistic regression analyses, the odds ratios per 10 nmol/l higher baseline vitamin D level were 0.95 (p < 0.05) and 0.94 (p = 0.01) for the development of the metabolic syndrome and hypercholesterolemia, respectively. There was no association between vitamin D and blood pressure. CONCLUSIONS: An optimal vitamin D status may influence cardiovascular health by changing the lipid profile in a favorable direction and decreasing the incidence of the metabolic syndrome.

All-Cause and Cardiovascular Mortality Among Insulin-Naïve People With Type 2 Diabetes Treated With Insulin Detemir or Glargine: A Cohort Study in the UK.

INTRODUCTION: Uncontrolled type 2 diabetes (T2D) is associated with an increased risk of micro- and macrovascular complications and mortality. The impact of basal insulins on the risks of mortality and cardiovascular mortality in people with T2D has not been thoroughly investigated in real-world settings. The aim of the present real-word study was to investigate differences in mortality among insulin-naïve people with T2D who initiated insulin detemir (detemir) and insulin glargine (glargine). METHODS: We assessed all-cause and cardiovascular mortality in people with T2D, aged ≥ 40 years and insulin-naïve at treatment initiation. People were identified from the United Kingdom Clinical Practice Research Datalink GOLD national database (2004-2019). Database information included prescribed medications, demographic and clinical variables and mortality. Cause of death was obtained from the Office for National Statistics (ONS). For mortality, 24 clinically relevant confounders were considered and adjusted for using Cox regression analyses. RESULTS: The total cohort included 12,847 people with T2D, including 3031 who commenced detemir and 9816 who commenced glargine. Median age was 66.8 years and median diabetes duration was 7.6 years. From the total cohort, 3231 deaths occurred during follow-up and 6897 people were eligible for linkage to the ONS for cardiovascular mortality data (528 cardiovascular deaths). The adjusted hazard ratio (HR) (95% confidence interval [CI]) was 0.86 (0.79; 0.95) for all-cause mortality and 0.83 (0.67; 1.03) for cardiovascular mortality, in favour of detemir versus glargine. These associations were more pronounced among people with obesity (body mass index ≥ 30 kg/m2), with HRs (95% CI) of 0.79 (0.69; 0.91) and 0.69 (0.50; 0.96) for all-cause and cardiovascular mortality, respectively. CONCLUSION: In this real-world observational study, there was an association between all-cause mortality and basal insulin choice in insulin-naïve people with T2D; the mortality risk was lower with detemir versus glargine after adjustment for potential confounders.

The association of ADH and ALDH gene variants with alcohol drinking habits and cardiovascular disease risk factors.

BACKGROUND: Genetic variation in ethanol metabolism may have an influence on both alcohol drinking habits and the susceptibility to health effects of alcohol drinking. Such influences are likely to bias exposure-disease associations in epidemiologic studies of health effects of alcohol drinking. In a Caucasian population, we examined the association of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) genetic variants with alcohol drinking habits, biomarkers of alcohol exposure, and risk factors for cardiovascular disease. METHODS: The study population consisted of 1,216 Danish men and women aged 15-77 years participating in a health examination in 1998. The health examination included a self-administered questionnaire (alcohol drinking habits), a physical examination (blood pressure), and various blood tests [alanine aminotransferase (ALAT), erythrocyte mean corpuscular volume (E-MCV), and lipids]. ADH and ALDH gene variants were determined by standard techniques. Data were analyzed by regression analyses adjusted for relevant confounders. RESULTS: Self-reported alcohol drinking was significantly associated with increasing levels of ALAT, E-MCV, high-density lipoprotein cholesterol, and blood pressure. The ALDH1b ala69val variant was associated with nondrinking and total alcohol intake. The ALDH2 promoter variant was associated with binge-drinking, and the ALDH1b1 ala69val polymorphism was associated with diastolic blood pressure. We did not find any statistically significant interactions between any of the gene variants and alcohol consumption in relation to the various outcomes. CONCLUSIONS: In this Caucasian population sample, we found evidence to support that genetic variation in ethanol metabolism may influence drinking habits, but no statistically significant gene-environment interactions. More large-scale epidemiologic studies are needed to confirm theses results and to further investigate genetic susceptibility to the effects of alcohol drinking.

IgE sensitization to inhalant allergens and the risk of airway infection and disease: A population-based study.

BACKGROUND: Immunoglobulin E (IgE) sensitization, which is the propensity to develop IgE antibodies against common environmental allergens, is associated with a lymphocyte T-helper type 2 (Th2) skewed immune response and a high risk of allergic respiratory disease. Little is known about whether IgE sensitization confers an increased risk of respiratory infections in adults. We investigated the association between IgE sensitization and the incidence of acute airway infections, other infections and chronic lower airway disease events as recorded in nation-wide registries. METHODS: We included 14,849 persons from five population-based studies with measurements of serum specific IgE positivity against inhalant allergens. Participants were followed by linkage to Danish national registries (median follow-up time 11.3 years). The study-specific relative risks were estimated by Cox regression analysis, meta-analysed, and expressed as hazard ratios, HRs (95% confidence intervals, CIs). RESULTS: The relative risks for IgE sensitized vs. non-sensitized were: for pneumonia (HR = 1.20, 95% CI: 1.01, 1.41), other acute airway infection (HR = 0.86, 95% CI: 0.60, 1.22), infection (HR = 1.06, 95% CI: 0.90, 1.24), asthma (HR = 2.26, 95% CI: 1.79, 2.86), and other chronic lower airway disease (HR = 1.31, 95% CI: 1.08, 1.58). In never smokers, the higher risk of pneumonia (HR = 1.73, 95% CI: 1.23, 2.44) and asthma (HR = 3.17, 95% CI: 2.10, 4.76) among IgE sensitized was more pronounced. CONCLUSIONS: IgE sensitization was associated with a higher risk of asthma, other chronic lower airway diseases, and pneumonia. However, the association between IgE sensitization and pneumonia may be explained by undiagnosed asthma causing the pneumonia. Further studies are needed for confirmation.

Longitudinal associations between lifestyle and vitamin D: A general population study with repeated vitamin D measurements.

Several lifestyle factors have been found to be associated with vitamin D status in cross-sectional studies, but it is not clear whether a change in these factors can actually affect the vitamin D level. We investigated the association between repeated measurements of physical activity, body mass index (BMI), diet, alcohol consumption, and smoking habits, and corresponding levels of vitamin D during 5 years of follow-up of a large general population sample. We included 4185 persons who participated and had vitamin D (serum-25-hydroxyvitamin D, 25-OH-D) measurements in the Inter99 study at baseline (1999-2001) and 5-year follow-up. In a subsample, 25-OH-D was also measured at 1- and 3-year follow-ups. We used mixed models to examine the association between repeated measurements of lifestyle factors and 25-OH-D levels. In multivariable analyses of repeated measurements, the difference in 25-OH-D was -0.32 ng/ml (95 % CI -0.37, -0.28) per 1 kg/m(2) increase in BMI; 4.50 ng/ml (95 % CI 3.84, 5.15) for persons moderately/vigorously physically active versus sedentary; 1.82 ng/ml (95 % CI 1.09, 2.56) for persons with healthy versus unhealthy dietary habits; 0.05 ng/ml (95 % CI 0.03, 0.07) per 1 standard drink/weak increase in alcohol consumption; and 0.86 ng/ml (95 % CI 0.36, 1.35) for never smokers versus daily smokers. Our study shows that lower BMI, a higher level of physical activity, a healthier diet and possibly a higher alcohol intake, and not smoking, are associated with higher 25-OH-D levels.

Prospective population-based study of the association between vitamin D status and incidence of autoimmune disease.

Beside its traditional role in skeletal health, vitamin D is believed to have multiple immunosuppressant properties, and low vitamin D status has been suggested to be a risk factor in the development of autoimmune disease. We investigated the association between vitamin D status and development of autoimmune disease. We included a total of 12,555 individuals from three population-based studies with measurements of vitamin D status (25-hydroxy vitamin D). We followed the participants by linkage to the Danish National Patient Register (median follow-up time 10.8 years). Relative risks of autoimmune disease were estimated by Cox regression and expressed as hazard ratios, HRs (95 % confidence intervals CIs). There were 525 cases of incident autoimmune disease. The risk for a 10 nmol/l higher vitamin D was: for any autoimmune disease (HR = 0.94 % CI 0.90, 0.98); thyrotoxicosis (HR = 0.83, 95 % CI 0.72, 0.96); type 1 diabetes (HR = 0.95, 95 % CI 0.88, 1.02), multiple sclerosis (HR = 0.89, 95 % CI 0.74, 1.07), iridocyclitis (HR = 1.00, 95 % CI 0.86, 1.17); Crohn's disease (HR = 0.95, 95 % CI 0.80, 1.13), ulcerative colitis (HR = 0.88, 95 % CI 0.75, 1.04); psoriasis vulgaris (HR = 0.99, 95 % CI 0.86, 1.13); seropositive rheumatoid arthritis (HR = 0.97, 95 % CI 0.89, 1.07), and polymyalgia rheumatica (HR = 0.94, 95 % CI 0.83, 1.06). We found statistically significant inverse associations between vitamin D status and development of any autoimmune disease and thyrotoxicosis in particular. Our findings suggest a possible protective role of a higher vitamin D status on autoimmune disease but warrant further studies to clarify causality.

Lifestyle-Related Factors and Atopy in Seven Danish Population-Based Studies from Different Time Periods.

BACKGROUND: The prevalence of allergic respiratory disease tends to increase in populations that adopt the so-called Westernized lifestyle. We investigated the association between atopy and several possible lifestyle-related factors in seven Danish population-based studies. METHODS: A total of 20048 persons participated in the seven studies. We used logistic regression to analyse the associations between possible determinants and atopy defined as serum specific IgE or skin prick test positivity against inhalant allergens. Associations were expressed as odds ratios (ORs) with 95% confidence intervals (95% CIs). In addition, individual participant data meta-analyses were performed. RESULTS: Atopy was significantly associated with younger age (OR per 1 year increase in age: 0.97; 95% CI: 0.97, 0.98); male sex (OR for males versus females: 1.34; 95% CI: 1.24, 1.45), heavy drinking (OR for heavy drinkers versus light drinkers: 1.15; 95% CI: 1.04, 1.27), never smoking (OR for current versus never smokers: 0.73; 95% CI: 0.67, 0.80), and higher educational level (OR for educated versus uneducated: 1.27; 95% CI: 1.15, 1.41). Atopy was not associated with blood pressure, serum total cholesterol, physical activity or body mass except in women only, where we found a positive association (OR for obese vs. normal weight: 1.18; 95% CI: 1.00, 1.39) with ptrend = 0.032. CONCLUSIONS: Of interest for preventive purposes, we found that atopy was associated with some of the reversible lifestyle-related factors that characterize a Westernized lifestyle.

The association of atopy with incidence of ischemic heart disease, stroke, and diabetes.

Allergy is a systemic inflammatory disease that could theoretically affect the risk of cardiovascular disease (CVD) and diabetes through inflammatory pathways or mast cell-induced coronary spasm. Whether allergy is associated with an increased risk of CVD and diabetes is largely unknown. We investigated the association between atopy as assessed by IgE sensitization, a well-accepted biomarker of allergy, and incidence of ischemic heart disease, stroke, and diabetes in five Danish population-based cohorts. A total of 14,849 participants were included in the study. Atopy was defined as serum-specific IgE positivity to inhalant allergens. The Danish National Diabetes Register enabled identification of incident diabetes. Likewise, the Danish Registry of Causes of Death and the Danish National Patient Register provided information on fatal and non-fatal ischemic heart disease and stroke. Data were analyzed by Cox regression analyses with age as underlying time axis and adjusted for study cohort, gender, education, body mass index, alcohol intake, smoking habits, physical activity during leisure time, serum lipids, and blood pressure. The prevalence of atopy was 26.9 % (n = 3,994). There were 1,170, 817, and 1,063 incident cases of ischemic heart disease, stroke, and diabetes, respectively (median follow-up 11.2 years). The hazard ratios, HRs (95 % confidence intervals, CIs) for atopics versus non-atopics: for ischemic heart disease (HR 1.00, 95 % CI 0.86, 1.16), stroke (HR 1.18, 95 % CI 0.99, 1.41), and diabetes (HR 1.06, 95 % CI 0.91, 1.23). Our results did not support the hypothesis that atopy is associated with higher risk of ischemic heart disease, stroke, or diabetes. However, a small-moderately increased risk cannot be excluded from our data.

Specific IgE positivity against inhalant allergens and development of autoimmune disease.

BACKGROUND: Allergic and autoimmune diseases have been suggested to be inversely associated. We investigated the association between atopy and development of any and specific types of autoimmune disease. METHODS: We included a total of 14,849 individuals from five population-based studies with measurements of atopy defined as specific IgE positivity against inhalant allergens. We followed the participants by linkage to the Danish National Patient Register (median follow-up time 11.2 years). Hazard ratio (HR) and 95% confidence interval (CI) of autoimmune disease were estimated by Cox regression. RESULTS: The risk for atopics versus non-atopics was: for any autoimmune disease (HR = 0.99, 95% CI: 0.83, 1.18), thyrotoxicosis (HR = 0.69, 95% CI: 0.34, 1.37), type 1 diabetes (HR = 1.16, 95% CI: 0.84, 1.60), multiple sclerosis (HR = 1.97, 95% CI: 0.95, 4.11), iridocyclitis (HR = 0.82, 95% CI: 0.38, 1.74), Crohn's disease (HR = 1.03, 95% CI: 0.47, 2.25), ulcerative colitis (HR = 0.93, 95% CI: 0.52, 1.69), psoriasis vulgaris (HR = 1.50, 95% CI: 0.86, 2.62), seropositive rheumatoid arthritis (HR = 0.74, 95% CI: 0.48, 1.14) and polymyalgia rheumatica (HR = 0.79, 95% CI: 0.44, 1.44). CONCLUSIONS: We found no statistically significant associations between atopy and autoimmune disease, but we cannot exclude relatively small to moderate effects - protective or promotive - of atopy on autoimmune disease.

Prospective population-based study of the association between serum 25-hydroxyvitamin-D levels and the incidence of specific types of cancer.

BACKGROUND: Observational studies have suggested an inverse association between vitamin D status and cancer. We investigated the prospective associations between vitamin D status and the total and specific type of cancer in three cohorts from the general Danish population. METHODS: A total of 12,204 individuals 18 to 71 years old were included. The level of 25-hydroxyvitamin D was measured at baseline, and information about cancer was obtained from the Danish Cancer Registry. RESULTS: During the 11.3-year median follow-up time, there were 1,248 incident cancers. HRs [95% confidence intervals (CI)] per 10 nmol/L higher baseline vitamin D level were: for all cancers (HR = 1.02; 95% CI, 0.99-1.04), all cancers excluding non-melanoma skin cancer, NMSC (HR = 1.00; 95% CI, 0.97-1.03), head and neck cancer (HR = 0.97; 95% CI, 0.84-1.12), colorectal cancer (HR = 0.95; 95% CI, 0.88-1.02), cancer of bronchus and lung (HR = 0.98; 95% CI, 0.91-1.05), breast cancer (HR = 1.02; 95% CI, 0.96-1.09), cancer of the uterus (HR = 1.10; 95% CI, 0.95-1.27), prostate cancer (HR = 1.00; 95% CI, 0.93-1.08), cancer of the urinary organs (HR = 1.01; 95% CI, 0.90-1.14), NMSC (HR = 1.06; 95% CI, 1.02-1.10), and malignant melanoma (HR = 1.06; 95% CI, 0.95-1.17). CONCLUSIONS: Apart from a significantly higher risk for NMSC with higher vitamin D status, we found no statistically significant associations between vitamin D status and total or specific cancers. IMPACT: Our results do not indicate that there is an impact of vitamin D on total cancer incidence.

Cause-specific mortality according to urine albumin creatinine ratio in the general population.

BACKGROUND: Urine albumin creatinine ratio, UACR, is positively associated with all-cause mortality, cardiovascular disease and diabetes in observational studies. Whether a high UACR is also associated with other causes of death is unclear. We investigated the association between UACR and cause-specific mortality. METHODS: We included a total of 9,125 individuals from two population-based studies, Monica10 and Inter99, conducted in 1993-94 and 1999-2001, respectively. Urine albumin creatinine ratio was measured from spot urine samples by standard methods. Information on causes of death was obtained from The Danish Register of Causes of Death until 31 December 2010. There were a total of 920 deaths, and the median follow-up was 11.3 years. RESULTS: Multivariable Cox regression analyses with age as underlying time axis showed statistically significant positive associations between UACR status and risk of all-cause mortality, endocrine nutritional and metabolic diseases, mental and behavioural disorders, diseases of the circulatory system, and diseases of the respiratory system with hazard ratios 1.56, 6.98, 2.34, 2.03, and 1.91, for the fourth UACR compared with the first, respectively. Using UACR as a continuous variable, we also found a statistically significant positive association with risk of death caused by diseases of the digestive system with a hazard ratio of 1.02 per 10 mg/g higher UACR. CONCLUSION: We found statistically significant positive associations between baseline UACR and death from all-cause mortality, endocrine nutritional and metabolic diseases, and diseases of the circulatory system and possibly mental and behavioural disorders, and diseases of the respiratory and digestive system.

Vitamin D status and chronic obstructive pulmonary disease: a prospective general population study.

OBJECTIVES: Vitamin D deficiency is common among persons with chronic obstructive pulmonary disease (COPD). Whether vitamin D affects the development and deterioration of COPD or is a consequence of the disease lacks clarity. We investigated the association between vitamin D status and prevalent and incident COPD in the general population. METHODS: We included a total of 12,041 individuals from three general population studies conducted in 1993-94, 1999-2001, and 2006-2008, respectively, with vitamin D measurements. Information on COPD was obtained from the Danish National Patient Register and The Danish Registry of Causes of Death. RESULTS: There were 85 prevalent and 463 incident cases of COPD (median follow-up 9.7 years). We found a statistically significant inverse association between vitamin D status and prevalent COPD with odds ratio = 0.89 (95% confidence interval, CI: 0.79, 1.0), but no statistically significant association with incident COPD with a hazard ratio = 0.98 (95% CI: 0.94, 1.0), respectively, per 10 nmol/l higher vitamin D status, when adjusted for possible confounders. CONCLUSIONS: We found a statistically significant inverse cross-sectional association between vitamin D status and COPD, but no association between vitamin D status and incident COPD.

Vitamin D status, liver enzymes, and incident liver disease and mortality: a general population study.

Vitamin D deficiency is common among patients with liver diseases. Both cholestatic and non-cholestatic liver diseases can cause vitamin D deficiency. Whether vitamin D status can also affect liver function is poorly understood. To investigate the association between vitamin D status, liver enzymes, and incident liver disease, we included a total of 2,649 individuals from the Monica10 study conducted in 1993-1994. Vitamin D status as assessed by serum 25-hydroxyvitamin, serum alanine transaminase (ALT), aspartate transaminase (AST), and gamma glutamyl transferase (GGT) were measured at baseline. Information on fatal and non-fatal liver disease was obtained from the Danish National Patient Register and The Danish Registry of Causes of Death, respectively. Median follow-up time was 16.5 years, and there were 62 incident cases of fatal and non-fatal liver disease. Multivariable Cox regression analyses with age as underlying time axis and delayed entry showed a statistically significant inverse association between vitamin D status and incident liver disease with a hazard ratio = 0.88 (95 % confidence interval 0.79-0.99) per 10 nmol/l higher vitamin D status at baseline (adjusted for gender, season, alcohol consumption, smoking, physical activity, dietary habits, education, body mass index, and ALT). The risk of having a high level of ALT, AST, or GGT tended to be higher for lower vitamin D levels, although not statistically significant. In this general population study, vitamin D status was inversely associated with incident liver disease. Further studies are needed to determine whether patients in risk of developing impaired liver function should be screened for vitamin D deficiency for preventive purposes.

Vitamin D status and incident cardiovascular disease and all-cause mortality: a general population study.

Low vitamin D status has been associated with cardiovascular disease (CVD) and mortality primarily in selected groups, smaller studies, or with self-reported vitamin D intake. We investigated the association of serum vitamin D status with the incidence of a registry-based diagnosis of ischemic heart disease (IHD), stroke, and all-cause mortality in a large sample of the general population. A total of 9,146 individuals from the two population-based studies, Monica10 and Inter99, were included. Measurements of serum 25-hydroxyvitamin D at baseline were carried out using the IDS ISYS immunoassay system in Monica10 and High-performance liquid chromatography in Inter99. Information on CVDs and causes of death was obtained from Danish registries until 31 December 2008. There were 478 cases of IHD, 316 cases of stroke, and 633 deaths during follow-up (mean follow-up 10 years). Cox regression analyses with age as underlying time axis showed a significant association between vitamin D status and all-cause mortality with a HR = 0.95 (P = 0.005) per 10 nmol/l higher vitamin D level. We found no association between vitamin D status and incidence of IHD or stroke (HR = 1.01, P = 0.442 and HR = 1.00, P = 0.920, respectively). In this large general population study, the observed inverse association between serum vitamin D status and all-cause mortality was not explained by a similar inverse association with IHD or stroke.

Vitamin D status and 5-year changes in urine albumin creatinine ratio and parathyroid hormone in a general population.

Vitamin D is associated with cardiovascular disease and renal function but the mechanisms are as yet unexplained. Microalbuminuria is associated with a higher risk of kidney function loss, cardiovascular disease, and mortality. Parathyroid hormone is a predictor of cardiovascular mortality and negatively correlated with glomerular filtration rate. We investigated the association between vitamin D status and 5-year changes in urine albumin creatinine ratio (UACR) and parathyroid hormone (PTH). A random sample of 6,784 individuals aged 30-60 years from a general population participated in the Inter99 study in 1999-2001. Vitamin D (serum-25-hydroxyvitamin D) was measured at baseline by high-performance liquid chromatography. UACR and PTH were measured at baseline and follow-up. Increased UACR was defined as UACR >4.0 mg/g reflecting the upper quartile at baseline. We included 4,330 individuals who participated at 5-year follow-up. In multivariable linear regression analysis, a 10-nmol/l higher baseline level of vitamin D was associated with a 5-year decrease in UACR by 0.92 % (95 % confidence interval, CI 0.13, 1.71). In multivariable logistic regression analysis, the odds ratio of developing increased UACR during follow-up was 0.96 (95 % CI 0.92, 0.98) per 10 nmol/l higher baseline vitamin D level. We found a significant inverse cross-sectional (p < 0.0001) but no prospective association (p = 0.6) between baseline vitamin D status and parathyroid hormone. We found low vitamin D status to be a predictor of long-term development of increased UACR. It remains to be proven whether vitamin D deficiency is a causal and reversible factor in the development of albuminuria.

Vitamin D status, filaggrin genotype, and cardiovascular risk factors: a Mendelian randomization approach.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

The relationship of glutathione-S-transferases copy number variation and indoor air pollution to symptoms and markers of respiratory disease.

INTRODUCTION: Exposure to particulate matter (PM) may induce inflammation and oxidative stress in the airways. Carriers of null polymorphisms of glutathione S-transferases (GSTs), which detoxify reactive oxygen species, may be particularly susceptible to the effects of PM. OBJECTIVES: To investigate whether deletions of GSTM1 and GSTT1 modify the potential effects of exposure to indoor sources of PM on symptoms and objective markers of respiratory disease. METHODS: We conducted a population-based, cross-sectional study of 3471 persons aged 18-69 years. Information about exposure to indoor sources of PM and respiratory symptoms was obtained by a self-administered questionnaire. In addition, measurements of lung function (spirometry) and fractional exhaled nitric oxide were performed. Copy number variation of GSTM1 and GSTT1 was determined by polymerase chain reaction-based assays. RESULTS: We found that none of the symptoms and objective markers of respiratory disease were significantly associated with the GST null polymorphisms. An increasing number of positive alleles of the GSTM1 polymorphism tended to be associated lower prevalence of wheeze, cough, and high forced expiratory volume in 1 s (FEV(1) ), but these trends were not statistically significant. Furthermore, we did not observe any statistically significant interactions between GST copy number variation and exposure to indoor sources of PM in relation to respiratory symptoms and markers. CONCLUSIONS: In this adult population, GST copy number variations were not significantly associated with respiratory outcomes and did not modify the effects of self-reported exposure to indoor sources of PM on respiratory outcomes.

Vitamin D status and cause-specific mortality: a general population study.

BACKGROUND: Vitamin D deficiency is associated with an increased risk of all-cause mortality in observational studies. The specific causes of death underlying this association lack clarity. We investigated the association between vitamin D status and cause-specific mortality. METHODS: We included a total of 9,146 individuals from the two population-based studies, Monica10 and Inter99, conducted in 1993-94 and 1999-2001, respectively. Vitamin D status was assessed as serum 25-hydroxyvitamin D. Information on causes of death was obtained from The Danish Register of Causes of Death until 31 December 2009. There were a total of 832 deaths (median follow-up 10.3 years). RESULTS: Multivariable Cox regression analyses with age as underlying time axis and vitamin D quartiles showed significant associations between vitamin D status and death caused by diseases of the respiratory system, the digestive system, and endocrine, nutritional and metabolic diseases with hazard ratios (HRs) 0.26 (p(trend) = 0.0042), 0.28 (p(trend) = 0.0040), and 0.21 (p(trend) = 0.035), respectively, for the fourth vitamin D quartile compared to the first. We found non-significantly lower HRs for death caused by mental and behavioural diseases and diseases of the nervous system, but no association between vitamin D status and death caused by neoplasms or diseases of the circulatory system. CONCLUSION: The associations of vitamin D status and cause-specific mortality suggest that we also look elsewhere (than to cardiovascular disease and cancer) to explain the inverse association between vitamin D status and mortality.