Tinnitus Is Marginally Associated with Body Mass Index, Heart Rate and Arterial Blood Pressure: Results from a Large Clinical Sample.

INTRODUCTION: This study aimed to explore whether body mass index (BMI), systolic blood pressure (RR syst), diastolic blood pressure (RR diast) or heart rate (HR) are associated with tinnitus status and/or severity. METHODS: To that end, we evaluated the influence of tinnitus status and Tinnitus Handicap Inventory (THI) score on BMI, RR syst, RR diast and HR by comparing data from a large sample of patients presenting to a specialized tertiary referral clinic (N = 1066) with data from a population-based control group (N = 9885) by means of linear models. RESULTS: Tinnitus patients had a significantly lower BMI and higher RR syst, RR diast and HR than non-tinnitus patients; however, the contribution of the case-control status to R2 was very small (0.1%, 0.7%, 1.4% and 0.4%, respectively). BMI had little predictive power for the THI score (higher BMI scores were related to higher THI scores; R2 = 0.5%) and neither RR syst, RR diast, nor HR showed a statistically significant association with THI. DISCUSSION: Our findings suggest that HR, RR and BMI are at most marginally associated with tinnitus status and severity.

Association of physical activity and sedentary behavior with type 2 diabetes and glycemic traits: a two-sample Mendelian randomization study.

INTRODUCTION: Observational studies suggest that physical activity lowers and sedentary behavior increases the risk of type 2 diabetes. Despite of some supportive trial data for physical activity, it is largely unresolved whether these relations are causal or due to bias. OBJECTIVE: We investigated the associations between accelerometer-based physical activity and sedentary behavior with type 2 diabetes and several glycemic traits using two-sample Mendelian randomization analysis. RESEARCH DESIGN AND METHODS: Single nucleotide polymorphisms (SNPs) associated at p<5×10-8 with accelerometer-based physical activity average accelerations, vigorous physical activity (fraction of accelerations >425 milligravities), and sedentary behavior (metabolic equivalent task ≤1.5) in a genome-wide analysis of the UK Biobank served as instrumental variables. OUTCOMES: Type 2 diabetes, hemoglobin A1c (HbA1c), fasting glucose, homeostasis model assessment of beta-cell function (HOMA-B), and homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: Physical activity and sedentary behavior were unrelated to type 2 diabetes, HbA1c, fasting glucose, HOMA-B, and HOMA-IR. The inverse variance weighted ORs per SD increment for the association between average accelerations and vigorous physical activity with type 2 diabetes were 1.00 (95% CI 0.94 to 1.07, p=0.948) and 0.83 (95% CI 0.56 to 1.23, p=0.357), respectively. These results were confirmed by sensitivity analyses using alternative MR-methods to test the robustness of our findings. CONCLUSIONS: Based on these results, genetically predicted objectively measured average or vigorous physical activity and sedentary behavior is not associated with type 2 diabetes risk or with glycemic traits in the general population. Further research is required to deepen the understanding of the biological pathways of physical activity.

Wnt5a: a potential factor linking psoriasis to metabolic complications.

Psoriasis is associated with comorbidity including obesity, insulin resistance and diabetes mellitus type 2. In obesity, the protein wingless-type MMTV integration site Family, Member 5a (wnt5a) is released from adipose tissue macrophages and was shown to be of importance in the development of insulin resistance. As wnt5a was also shown to be upregulated in psoriatic skin lesions, we investigated whether wnt5a and its counterpart secreted frizzled-related protein 5 are altered in the circulation of lean and obese patients with psoriasis compared with lean and obese healthy volunteers by measuring serum concentrations of both proteins. Our results showed that wnt5a was significantly higher in lean patients with psoriasis (0.096 ng/ml; SD 0.12) compared with lean healthy controls (0.020 ng/ml; SD 0.04; P ≤ 0.01) as well as in obese patients (0.177 ng/ml; SD 0.14) compared with obese healthy controls (0.011 ng/ml; SD 0.03; P ≤ 0.001). Therefore, we suggest that in psoriasis, an increase in wnt5a may contribute to the development of metabolic comorbidity.

Cardiovascular biomarkers in patients with psoriasis.

Psoriasis is a systemic inflammatory disease of the skin with associated comorbidity. Severe forms of psoriasis are associated with increased mortality, which might be due to cardiovascular (CV) comorbidity. In this study, we investigated in 79 patients with psoriasis compared to 80 healthy volunteers different biomarkers that play a role in vascular disease and inflammation, such as C-reactive protein (CRP), human soluble CD40 ligand (sCD40L), oxidized low-density lipoprotein (ox-LDL), human matrix Gla protein (MGP) and fetuin-A. Our results showed that CRP (P < 0.0001), sCD40L (P < 0.0001) and MGP (P < 0.0001) were increased in the patient cohort. Fetuin-A showed decreased serum levels in patients with psoriasis (P < 0.0001), whereas ox-LDL did not show any significant difference. In multivariate analyses controlling for sex, age and BMI, these findings were confirmed. Thus, CV biomarkers are altered in patients with psoriasis. If the decrease in fetuin-A as well as the increase in sCD40L can be proven in further studies, these biomarkers may help to characterize a subgroup of patients who are at risk to develop CVD and/or monitor the effect of therapeutic antipsoriatic strategies on concomitant diseases. This knowledge may be useful in the management of high-need patients with psoriasis.

Nuclear pregnane X receptor single nucleotide polymorphism (-25385C/T) is not associated with inflammatory bowel disease in pediatric patients.

OBJECTIVE: Studies in adults characterized the role of the pregnane X receptor (PXR) in the pathophysiology of inflammatory bowel disease (IBD) with conflicting results; pediatric studies are still lacking. PATIENTS AND METHODS: Genotyping for the -25385C/T polymorphism of the PXR gene in 187 white children with IBD and 185 controls. Determination of colonic PXR expression in selected patients with IBD. RESULTS: Minor allele frequency was seen in 35.6% patients with IBD and 40.5% controls (P = 0.174), although no significant differences were seen between the genotypes (P = 0.366). PXR was underexpressed in colonic tissue of 7 out of 11 Crohn disease and in 4 out of 5 patients with ulcerative colitis. CONCLUSIONS: We could not confirm an association of the -25385C/T polymorphism in pediatric patients with IBD.

Prevalence and incidence of the metabolic syndrome in the European Lacidipine Study on Atherosclerosis (ELSA) and its relation with carotid intima-media thickness.

BACKGROUND: The European Lacidipine Study on Atherosclerosis (ELSA) randomized 2334 hypertensive patients to either the lipophilic calcium antagonist lacidipine or the beta-blocker atenolol for 4 years. About 35% of subjects in both groups received additional hydrochlorothiazide (12.5-25 mg/day). The patients were followed up for carotid intima-media thickness (IMT) changes for 3.7 years. OBJECTIVES: The present post-hoc analyses were aimed at: describing the prevalence of the metabolic syndrome (MS) at baseline; investigating the effect of long-term antihypertensive therapy (and separately of atenolol and lacidipine) on MS prevalence; exploring whether MS at baseline influenced changes in carotid IMT and incidence of cardiovascular events during treatment; and describing the relations between MS and new cases of diabetes developing during treatment. METHODS: At baseline 2034 patients had, in addition to blood pressure (BP), measurements of blood glucose, serum high-density lipoprotein (HDL)-cholesterol, triglycerides and body mass index (BMI > 28.8 for men and > 26.2 for women were taken to correspond to waist circumference > 102 and > 88 cm, respectively). These measurements were repeated after 4 years of treatment in 1444 patients. MS was defined according to Adults Treatment Panel III (ATP III). RESULTS: A high proportion of ELSA patients (33.3%) had MS at baseline, with no difference between atenolol and lacidipine. Baseline IMT was slightly greater in MS patients, but only the difference in mean maximum IMT at common carotids and bifurcations (CBMmax) achieved significance (P = 0.0325). Progression of CBMmax was also slightly greater in MS patients (P = 0.0241), but significance was lost when adjusted for covariates. No significant difference was found in the incidence of new cardiovascular events between patients with and without MS. The incidence of new MS was 21.4%, and significantly greater in patients under atenolol (25.2%) than lacidipine (17.7%; P = 0.0045). New-onset diabetes occurred in 5.54% of ELSA patients, and was three times higher among patients with than those without MS (10.28 versus 3.43%, P > 0.0001). CONCLUSIONS: Our analyses show a high prevalence of MS in ELSA hypertensives, a substantial incidence of new cases of MS and diabetes, the latter mostly among patients with MS. These analyses also show that in ELSA lacidipine was superior to atenolol, not only in showing a lower progression of carotid atherosclerosis, but also in causing a significantly lower incidence of new MS.

Association of a CXCL9 polymorphism with pediatric Crohn's disease.

Genetic and environmental factors contribute to the etiopathogenesis of Crohn's disease (CD) and ulcerative colitis (UC). To identify new susceptibility genes, we determined the mRNA expression level of 88 genes from different biological contexts on colonic biopsies of CD and UC patients. We show that CXCL9 was overexpressed in colonic tissue of 3/5 CD and 3/3 UC patients compared to healthy controls. SNP genotyping for the 77147452G-->A polymorphism of the CXCL9 gene on 114 pediatric IBD patients and 120 ethnically matched unaffected adults detected a minor allele frequency of 20.3% in CD patients compared to 31.3% in controls (p=0.016). Strikingly, children with homozygosity for the wild-type allele had a significant earlier onset of CD than heterozygous individuals (11.1 versus 13.8 years). This is the first report of inverse association of the CXCL9 77147452G-->A polymorphism with pediatric CD. Our data may contribute to a better understanding of the pathophysiology underlying CD.

Association of NOD1 polymorphisms with atopic eczema and related phenotypes.

BACKGROUND: Interactions with microbial pathogens are crucial for the maturation of the immune system. The nucleotide-binding oligomerization domain protein 1 (NOD1) is a cytosolic receptor sensing a muropeptide found mostly in gram-negative bacterial peptidoglycans. NOD1 is located on chromosome 7p14-p15, a region that has been linked with atopy. Recently, polymorphisms of the closely related NOD2 have been associated with atopy-related traits. OBJECTIVES: Within a large population-based cohort of German adults (n = 1417), a case-control population for atopic eczema (n = 454), and a large cohort of parent-offspring trios for atopic eczema (189 trios), we evaluated 11 NOD1 polymorphisms for associations with atopic phenotypes. Methods Subjects were phenotyped by standardized questionnaires and interviews, skin examination, and serum IgE measurements. Genotyping was performed by using matrix-assisted laser desorption ionization-time of flight mass spectrometry. RESULTS: Analyses revealed significant association of one NOD1 haplotype with atopic eczema in the population-based cohort ( P = .004) and the case-control population ( P = .003). Another NOD1 haplotype was associated with decreased total IgE ( P = .008). In addition, significant associations with total serum IgE levels were observed for polymorphisms rs2907748 ( P = .006), rs2907749 ( P = .012), and rs2075822 ( P = .018). These polymorphisms were significantly associated with atopic eczema and asthma in the family-based association analyses ( P = .001-.043). Seven polymorphisms showed significant transmission distortion for total IgE levels ( P values < .0001-.029). CONCLUSION: These data indicate that genetic variants within NOD1 are important determinants of atopy susceptibility.