RADseq data reveal a lack of admixture in a mouse lemur contact zone contrary to previous microsatellite results.

Microsatellites have been a workhorse of evolutionary genetic studies for decades and are still commonly in use for estimating signatures of genetic diversity at the population and species level across a multitude of taxa. Yet, the very high mutation rate of these loci is a double-edged sword, conferring great sensitivity at shallow levels of analysis (e.g. paternity analysis) but yielding considerable uncertainty for deeper evolutionary comparisons. For the present study, we used reduced representation genome-wide data (restriction site-associated DNA sequencing (RADseq)) to test for patterns of interspecific hybridization previously characterized using microsatellite data in a contact zone between two closely related mouse lemur species in Madagascar (Microcebus murinus and Microcebus griseorufus). We revisit this system by examining populations in, near, and far from the contact zone, including many of the same individuals that had previously been identified as hybrids with microsatellite data. Surprisingly, we find no evidence for admixed nuclear ancestry. Instead, re-analyses of microsatellite data and simulations suggest that previously inferred hybrids were false positives and that the program NewHybrids can be particularly sensitive to erroneously inferring hybrid ancestry. Combined with results from coalescent-based analyses and evidence for local syntopic co-occurrence, we conclude that the two mouse lemur species are in fact completely reproductively isolated, thus providing a new understanding of the evolutionary rate whereby reproductive isolation can be achieved in a primate.

Antibodies against potassium channel interacting protein 2 induce necrosis in isolated rat cardiomyocytes.

Auto-antibodies against cardiac proteins have been described in patients with dilated cardiomyopathy. Antibodies against the C-terminal part of KChIP2 (anti-KChIP2 [C-12]) enhance cell death of rat cardiomyocytes. The underlying mechanisms are not fully understood. Therefore, we wanted to explore the mechanisms responsible for anti-KChIP2-mediated cell death. Rat cardiomyocytes were treated with anti-KChIP2 (C-12). KChIP2 RNA and protein expressions, nuclear NF-κB, mitochondrial membrane potential Δψm, caspase-3 and -9 activities, necrotic and apoptotic cells, total Ca(2+) and K(+) concentrations, and the effects on L-type Ca(2+) channels were quantified. Anti-KChIP2 (C-12) induced nuclear translocation of NF-κB. Anti-KChIP2 (C-12)-treatment for 2 h significantly reduced KChIP2 mRNA and protein expression. Anti-KChIP2 (C-12) induced nuclear translocation of NF-κB after 1 h. After 6 h, Δψm and caspase-3 and -9 activities were not significantly changed. After 24 h, anti-KChIP2 (C-12)-treated cells were 75 ± 3% necrotic, 2 ± 1% apoptotic, and 13 ± 2% viable. Eighty-six ± 1% of experimental buffer-treated cells were viable. Anti-KChIP2 (C-12) induced significant increases in total Ca(2+) (plus 11 ± 2%) and K(+) (plus 18 ± 2%) concentrations after 5 min. Anti-KChIP2 (C-12) resulted in an increased Ca(2+) influx through L-type Ca(2+) channels. In conclusion, our results suggest that anti-KChIP2 (C-12) enhances cell death of rat cardiomyocytes probably due to necrosis.

Optimizing centrifugation of coagulation samples in laboratory automation.

BACKGROUND: High acceleration centrifugation conditions are used in laboratory automation systems to reduce the turnaround time (TAT) of clinical chemistry samples, but not of coagulation samples. This often requires separate sample flows. The CLSI guideline and manufacturers recommendations for coagulation assays aim at reducing platelet counts. For measurement of prothrombin time (PT) and activated partial thromboplastin time (APTT) platelet counts (Plt) below 200×10(9)/L are recommended. Other coagulation assays may require even lower platelet counts, e.g., less than 10 × 10(9)/L. Unifying centrifugation conditions can facilitate the integration of coagulation samples in the overall workflow of a laboratory automation system. METHODS: We evaluated centrifugation conditions of coagulation samples by using high acceleration centrifugation conditions (5 min; 3280×g) in a single and two consecutive runs. RESULTS of coagulation assays [PT, APTT, coagulation factor VIII (F. VIII) and protein S] and platelet counts were compared after the first and second centrifugation. RESULTS: Platelet counts below 200×10(9)/L were obtained in all samples after the first centrifugation and less than 10 × 10(9)/L was obtained in 73% of the samples after a second centrifugation. Passing-Bablok regression analyses showed an equal performance of PT, APTT and F. VIII after first and second centrifugation whereas protein S measurements require a second centrifugation. CONCLUSIONS: Coagulation samples can be integrated into the workflow of a laboratory automation system using high acceleration centrifugation. A single centrifugation was sufficient for PT, APTT and F. VIII whereas two successive centrifugations appear to be sufficient for protein S activity.

Are serum TSH levels associated with oxidized low-density lipoprotein? Results from the Study of Health in Pomerania.

OBJECTIVE: Oxidized LDL (oxLDL) is involved in the pathogenesis of atherosclerosis. Thus, it is important to investigate putative risk factors for increased oxLDL. Evidence suggests that, compared to euthyroid individuals, LDL-cholesterol (LDL-C) levels are lower in individuals with overt hyperthyroidism. Whereas oxidization of LDL-C into oxLDL is increased in overt hyper- and hypothyroidism, it has not been investigated whether subclinical thyroid dysfunction impacts on oxLDL levels in general. We have analysed the association between serum thyrotrophin (TSH) levels and oxLDL in a population-based study. DESIGN, PATIENTS AND MEASUREMENTS: Of the 4308 individuals enrolled in the Study of Health in Pomerania, data from 3519 individuals were analysed (680 missing the oxLDL variable). oxLDL was measured by the oxLDL competitive ELISA on a BEP 2000. Multivariable linear regression models were performed to assess the association between serum TSH and oxLDL levels. RESULTS: TSH was positively associated with oxLDL in a curvilinear fashion with increasing serum TSH levels. Subgroup analyses revealed a significant association only in the group of individuals >60 years. Additionally, serum TSH levels were not associated with the ratio of oxLDL to LDL (ß = -0·04; 95% CI = -0·08, 0·01; P = 0·084). CONCLUSIONS: We demonstrate an association between serum TSH and oxLDL levels especially in the range of subclinical thyroid disease. Our study suggests that serum TSH levels affect LDL-C production or clearance rather than the LDL-C oxidation processes.

Common carotid intima-media thickness and framingham risk score predict incident carotid atherosclerotic plaque formation: longitudinal results from the study of health in Pomerania.

BACKGROUND AND PURPOSE: Cross-sectional studies describe a positive association between common carotid artery intima-media thickness (CCA-IMT) and carotid plaques (CP). However, longitudinal data on the predictive value of CCA-IMT for occurrence of CP are limited. Therefore, the role of increasing CCA-IMT in the atherosclerotic process is still discussed controversially. METHODS: We investigated the predictive value of CCA-IMT and the Framingham risk score (FRS) for incident CP formation in a population-based longitudinal study of 1922 subjects aged 45 to 81 years who underwent ultrasonography of both carotid arteries and received vascular risk factor assessment at baseline and after 5 years. CP was defined as any protruding focal thickening of the intima-media complex. Incident CP formation during follow-up was defined as the appearance of at least 1 CP in a previously plaque-free arterial segment (right and left common, internal, and external carotid arteries and carotid bifurcation). RESULTS: Among the 636 subjects without CP at baseline, 418 (66%) had at least 1 incident CP during follow-up. In a multivariable negative binominal regression model adjusted for age, gender, and the FRS, the number of arterial segments affected by incident CP was 1.53-fold higher (CI, 1.12-2.07; P<0.01) for subjects in the highest quartile of the overall CCA-IMT distribution compared to those in the lowest quartile. CONCLUSIONS: Both CCA-IMT and FRS independently predict incident CP formation. The risk of CP formation may actually be underestimated in subjects with low FRS and high IMT.

Reference intervals for eight measurands of the blood count in a large population based study.

BACKGROUND: The blood count is widely used in clinical practice. Well defined reference intervals for each measurand are essential for correct clinical interpretation of results. Most previous studies have not been population-based. We therefore calculated reference intervals for several hematological measurands from a sample of the general adult population of Northeastern Germany. METHODS AND RESULTS: We used data from 2967 healthy individuals recruited for the population-based Study of Health in Pomerania (SHIP). Reference intervals were calculated according to the guidelines of the Clinical and Laboratory Standards Institute (CLSI) using the bootstrap method for the age range from 20 to 79 years and, in addition, stratified according to age and gender with both bootstrap and quantile regression procedures. Reference ranges for erythrocytes, hemoglobin and hematocrit increased with age in women but decreased in men. CONCLUSIONS: Our reference intervals were lower than those previously published for erythrocytes, hemoglobin, hematocrit and leukocytes but higher for Mean Corpuscular Volume (MCV) and Mean Corpuscular Hemoglobin (MCH). Different laboratory methods and study populations may lead to disparity in results.

A descriptive analysis of relations between parents' self-reported smoking behavior and infants' daily exposure to environmental tobacco smoke.

BACKGROUND: The aims of the present study were to examine relations between parents' self-reported smoking behavior and infants' daily exposure to environmental tobacco smoke, as assessed by urinary cotinine-to-creatinine ratio (CCR), and to describe the CCR over seven days among infants at home. METHODS: A convenience sample of 27 households was drawn. Each household had to have at least one daily tobacco smoker and one child up to three years of age. Over a seven-day period, urine samples were obtained from the child daily. To examine relations between parents' self-reported smoking and infants' daily CCR, generalized estimating equation (GEE) analysis was used. RESULTS: The data revealed that infants from households with indoor smoking had higher CCRs than infants in households with outdoor smoking. CCRs were higher in girls than in boys. Older infants had lower CCRs than younger infants. Smoking outside the home versus inside the home, infant's gender, and infants' age accounted for 68% of the variance in CCR in a GEE data analysis model. No increase or decrease of CCR over time was found. CONCLUSION: The findings suggest that parents' self-reported smoking indoors at home versus outdoors is predictive of CCR among infants three and younger. Higher CCR concentrations in girls' urine need further examination. Furthermore, significant fluctuations in daily CCR were not apparent in infants over a seven-day time period.

Regional differences in the prevalence of left ventricular hypertrophy within Germany.

BACKGROUND: There are considerable regional disparities in the prevalence of cardiovascular risk factors within Germany. We undertook this study to investigate differences in the prevalence of left ventricular hypertrophy (LVH) between northeast and southwest Germany. METHODS: Data from two population-based studies, Kooperative Gesundheitsforschung im Raum Augsburg (KORA) conducted in southwest and Study of Health in Pomerania (SHIP) conducted in northeast Germany, were utilized. The study population comprised 2,516 women and men (835 from KORA and 1,681 from SHIP) aged 45-74 years who had no history of myocardial infarction. Echocardiograms were obtained according to standard protocols. Left ventricular mass (LVM), left ventricular mass indexed for body height, and left ventricular hypertrophy were used as dependent variables in multivariable analyses. RESULTS: SHIP participants had higher LVM and left ventricular mass index values compared with KORA participants. These differences remained after analyses were adjusted for major confounders including obesity and hypertension. Consequently, there were higher proportions of LVH in SHIP compared with KORA across all 10-year age groups. Multivariable logistic regression revealed that the odds for LVH in participants living in northeast Germany were higher in women and men, respectively, by 1.57 (95% confidence interval: 1.18-2.09) and 1.68 (95% confidence interval: 1.25-2.27) than in participants living in southwest Germany. Potential methodological differences between studies do not seem to account for these findings. CONCLUSION: There is a higher prevalence of LVH in northeast compared with southwest Germany. Regional disparities in hypertension and overweight only partly explain this difference.

Dose-dependent titration of prorenin and blood pressure in Cyp1a1ren-2 transgenic rats: absence of prorenin-induced glomerulosclerosis.

OBJECTIVE: Prorenin has been associated with cardiovascular disease and the development of glomerulosclerosis via a renin/prorenin receptor. In cyp1a1ren-2 transgenic rats, prorenin levels and arterial pressure can be increased by oral administration of indole-3-carbinol (I3C). The transgenic strain has been used as a model of malignant hypertension. METHODS: The present study was designed to test the hypotheses that (i) low doses of I3C would result in dose-dependent sustained increases in arterial pressure without signs of malignancy, making cyp1a1ren-2 transgenic rats a useful model to study nonmalignant hypertension, and (ii) cyp1a1ren-2 transgenic rats would develop glomerulosclerosis when they were chronically exposed to 0.125% I3C in their diet. RESULTS: I3C treatment for 2 weeks resulted in increases of plasma prorenin concentrations and arterial pressure in a dose-dependent manner. Rats thrived well over a period of 12 weeks on dietary I3C concentrations (wt/wt) of 0.125%. Plasma prorenin concentration rose from 0.1 +/- 0.1 microg to 17.9 +/- 5.0 mug angiotensin I/ml per h (P < 0.01) and mean arterial pressure increased to a plateau of 170 +/- 5 mmHg (P < 0.001) between weeks 6 and 12. After 12 weeks of 0.125% I3C, rats exhibited moderate hypertensive renal vasculopathy, but no histological signs of glomerulosclerosis. CONCLUSIONS: The cyp1a1ren-2 transgenic rat model allows for chronic dose-dependent titration of arterial pressure by a simple and non-invasive intervention, making this strain a useful model to study malignant and nonmalignant arterial hypertension. High circulating prorenin levels per se do not cause glomerulosclerosis.

Reference ranges of serum IGF-1 and IGFBP-3 levels in a general adult population: results of the Study of Health in Pomerania (SHIP).

OBJECTIVE: Insulin-like growth factor I (IGF-1), which is mostly carried by IGF binding protein 3 (IGFBP-3), mediates endocrine actions of growth hormone and represents an important prognostic factor for systemic diseases. The main objectives of the present study were (1) to calculate age- and sex-specific reference values for serum IGF-1 and IGFBP-3 levels using the Gaussian mean+/-1.96 *standard deviation method and the quantile regression method and (2) to perform a comparison of the results from both statistical methods. DESIGN: Cross-sectional study (Study of Health in Pomerania). The study population included 2499 men and women aged 20-79 years. METHODS: Serum IGF-1 and IGFBP-3 levels were determined by chemiluminescence immunoassays. Linear and quantile regressions were performed to calculate age- and sex-related reference ranges. RESULTS: Both statistical methods generated different results: The reference ranges based on linear regression identified 43 (1.7%) subjects with serum IGF-1 levels and 99 (4.0%) subjects with serum IGFBP-3 levels outside the reference range. Using quantile regression, 117 (4.7%) or 118 subjects (4.7%) with serum IGF-1 or IGFBP-3 levels outside the range were detected, respectively. CONCLUSION: The present study established age- and sex-specific reference ranges for serum IGF-1 and IGFBP-3 levels. Quantile regression should be preferred to calculate reference ranges because a better concordance to original data is possible due to no distribution assumption are required and the robustness against outliers is given.

Inverse association between periodontitis and respiratory allergies in patients with type 1 diabetes mellitus.

AIM: In a general adult population, we have demonstrated an inverse association between periodontitis and respiratory allergies that is in line with the hygiene hypothesis suggesting a protective effect of infections against the development of allergies. The objective of the present study was to investigate the association between periodontitis and respiratory allergies in a type 1 diabetes mellitus population. MATERIAL AND METHODS: The study population comprised 170 patients with type 1 diabetes mellitus aged 17-80 years. Respiratory allergies were present in 22 subjects. The attachment loss (AL) was measured. Periodontitis was defined according to the percentage of surfaces that exceeded 3 mm AL (healthy, mild, moderate, severe periodontal conditions). RESULTS: Our adjusted analyses revealed an inverse association between periodontitis and respiratory allergies. For increasing AL, a trend towards a decreasing risk was present for respiratory allergies (p(trend)<0.05). Compared with subjects with healthy periodontal conditions, individuals with severe periodontal conditions had the lowest risk of respiratory allergies [odds ratios (OR) 0.06 (95% confidence interval (CI) 0.01-0.39)], followed by subjects with moderate AL [OR 0.14 (95% CI 0.03-0.63)] and mild AL [OR 0.32 (95% CI 0.09-1.08)]. CONCLUSION: There is a strong inverse association between periodontitis and respiratory allergies in patients with type 1 diabetes mellitus. These findings further support the hygiene hypothesis.

No association of seropositivity for anti-Borrelia IgG antibody with mental and physical complaints.

Undiagnosed chronic Lyme disease caused by Borrelia burgdorferi is considered a differential diagnoses in medically unexplained symptoms like arthralgias, distal paresthesias, depressive symptoms, lack of concentration and fatigue. The aims of the study were to assess the association of mental and physical complaints with seropositivity for anti-Borrelia IgG in a general population sample. Seropositivity indicated an infection with Borrelia in the past. The Study of Health in Pomerania was conducted in a community living in a region with endemic Lyme disease. Mental and physical complaints were assessed on 38 items with the von Zerssen's complaint scale. IgG antibodies to Borrelia were determined by ELISA in 4264 individuals. Seropositivity was analyzed applying two cut-off scores (>5 and >10 IU/ml). IgG antibodies to Borrelia were found positive in 388 subjects (9.1%) applying the >5 IU/ml cut-off and in 130 subjects (3.0%) applying the >10 IU/ml cut-off. In multivariate analyses (MANCOVA), both definitions of seropositivity were not associated with increased mental or physical complaints while adjusting for gender, age, employment status, rural residency, physical activity, diabetes mellitus and number of chronic diseases. In the general population, seropositivity for anti-Borrelia IgG antibodies was not associated with an increase of self-rated mental or physical complaints or impairments. Therefore, clinicians should not overvalue seropositivity for anti-Borrelia IgG as a medical cause for unexplained mental or physical complaints.

Association between serum insulin-like growth factor-I levels and thyroid disorders in a population-based study.

OBJECTIVE: There is current debate on whether serum IGF-I levels are associated with thyroid disorders. The aims of the present study were: 1) to investigate possible associations between serum IGF-I levels and thyroid disorders and 2) to analyze the role of serum IGF binding protein (IGFBP)-3 and TSH levels for these associations. DESIGN: This was a cross-sectional Study of Health in Pomerania. SETTING: The study was conducted in the general population of northeast Germany. SUBJECTS: The study population comprised 3662 subjects (1746 women) without history of thyroid disorders. INTERVENTIONS: No interventions have been performed. MAIN OUTCOME MEASURES: Goiter and thyroid nodules were determined by ultrasound. Serum TSH levels less than 0.25 mIU/liter were considered decreased. RESULTS: Adjusted for major confounders and risk factors for thyroid disorders, subjects with serum IGF-I levels above the upper tertile had higher odds for goiter relative to subjects with serum IGF-I levels below the lower tertile [odds ratio (OR) 1.67; 95% confidence interval (CI) 1.24-2.26 in women; OR 2.04; 95% CI 1.55-2.68 in men]. A similar association was present for thyroid nodules in men (OR 1.64; 95% CI 1.17-2.32) and for decreased serum TSH levels in women (OR 1.65; 95% CI 1.00-2.69). Serum IGFBP-3 levels were not associated with thyroid disorders and did not represent effect modifiers for the association between serum IGF-I levels and the endpoints. CONCLUSIONS: We conclude that high serum IGF-I levels are associated with goiter. Whereas high serum IGF-I levels are also related to thyroid nodules in men, they are related to decreased serum TSH levels in women. Serum IGFBP-3 and TSH levels did not modulate these associations.

Seropositivity for anti-Borrelia IgG antibody is independently associated with carotid atherosclerosis.

BACKGROUND: Various infectious agents are associated with atherosclerosis. This analysis was performed to investigate relation between seropositivity for anti-Borrelia IgG and carotid atherosclerosis. METHODS: The cross-sectional Study of Health in Pomerania was conducted in a general community living in a region with endemic Lyme disease. A random sample of 2483 individuals aged 45-79 years was available for the present analysis. Carotid atherosclerosis was sonographically assessed as intima-media thickness of the common carotid artery and as prevalent atherosclerotic plaques in the extracranial carotid arteries. IgG antibodies to Borrelia were determined by ELISA. RESULTS: IgG antibodies to Borrelia were found positive (> 10 IU/mL) in 108 subjects (4.3%). Persons with and without positive anti-Borrelia IgG antibodies differed with respect to carotid intima-media thickness values (0.863 +/- 0.017 mm versus 0.792 +/- 0.004 mm; p < 0.001) and prevalent carotid plaques (odds ratio 2.65, 95% confidence interval 1.53-4.61; p = 0.001), respectively. Seropositivity for anti-Borrelia IgG was also associated with both atherosclerotic endpoints when age, sex and further atherogenic risk factors and confounders were included in multivariable statistical models. CONCLUSIONS: In a region with endemic Lyme disease, seropositivity for anti-Borrelia IgG antibodies is independently associated with atherosclerosis. Our findings add support to the hypothesis that exposure to infectious pathogens increases the atherosclerosis risk.

Regional disparities of hypertension prevalence and management within Germany.

OBJECTIVE: To investigate regional variations in the prevalence and management of hypertension in two communities in the north-east and the south-west of Germany. STUDY SETTING: Two population-based surveys of men and women aged 25-74 years, using a common standardized protocol: the Study of Health in Pomerania (SHIP; 3744 participants) and the Kooperative Gesundheitsforschung in der Region Augsburg (KORA; 4224 participants). MAIN OUTCOME MEASURES: Comparison of SHIP and KORA with regard to mean systolic (SBP) and diastolic blood pressure (DBP), prevalence of hypertension, percentage of awareness, treatment and control of hypertension in the community, by age and sex. RESULTS: The overall age-standardized prevalence of hypertension for men was 60.1% in SHIP and 41.4% in KORA; the corresponding values for women were 38.5 and 28.6%. Mean blood pressure differences were present in each 10-year age group and sex. The overall SBP difference between SHIP and KORA was 8.2 mmHg (95% confidence interval 7.2-9.3) in men and 6.3 mmHg (5.3-7.3) in women, the respective DBP differences were 3.8 mmHg (3.2-4.5) and 3.6 mmHg (3.0-4.2). Nevertheless, the percentage of awareness, treatment and control of hypertension was strikingly similar in the two studies (women, P = 0.858; and men, P = 0.564). CONCLUSIONS: The entire distribution of diastolic and systolic blood pressure values was shifted upwards in the north-eastern as compared to the south-western German population samples and the prevalences of hypertension differed accordingly. Despite such substantial epidemiologic differences, the community management of hypertension was of almost identical quality.

Relation of parity with common carotid intima-media thickness among women of the Study of Health in Pomerania.

BACKGROUND AND PURPOSE: Metabolic and hormonal changes associated with pregnancy and childbirth are assumed to contribute to the development of cardiovascular disease among women. We analyzed the association of parity with common carotid intima-media thickness (IMT), which has a predictive value of subsequent myocardial infarction and stroke. METHODS: The Study of Health in Pomerania (SHIP), an epidemiological study of the general population in the northeast of Germany, included 1195 women aged 45 to 79 years. Mean and maximum far-wall IMT of the common carotid arteries were assessed by high-resolution ultrasound. All women were comprehensively characterized as to their reproductive history as well as to socioeconomic, behavioral, and biological risk factors. RESULTS: There was a U-shaped association between the number of children (from 0 to > or =4) and mean and maximum IMT. Nulliparous women had the highest age-adjusted mean (0.81 mm [95% CI, 0.78 to 0.84]) and maximum IMT (1.04 mm [95% CI, 1.00 to 1.09]), and women with single parity the lowest (mean IMT, 0.73 [95% CI, 0.72 to 0.74]; maximum IMT, 0.91 mm [95% CI, 0.89 to 0.93]; P<0.001 versus nulliparity for both parameters). Stepwise multivariate adjustment for socioeconomic factors, lifestyle variables, and biological variables attenuated the magnitude of this association yet significance remained. CONCLUSIONS: Nulliparity and higher number of children are associated with increased carotid IMT. These findings add support to the hypothesis of a link between the reproductive history of women and cardiovascular disease.

The association of thyroid function with cardiac mass and left ventricular hypertrophy.

Decreased serum TSH levels predict cardiovascular mortality, which could be explained by left ventricular hypertrophy (LVH). The aim of this analysis was to investigate the association between thyroid function and LVH. The population-based Study of Health in Pomerania was conducted in a previously iodine-deficient area. Data of 1510 individuals at least 45 yr of age with echocardiography and without thyroid disorders were analyzed. LVH was defined as a left ventricular mass index (LVMI) exceeding 150 g/m(2) (men) or 120 g/m(2) (women). Overt hyperthyroidism was associated with LVMI (P < 0.01), whereas euthyroid subjects and those with elevated TSH levels did not significantly differ with regard to LVMI. LVH was observed in three (15.0%) subjects with elevated serum TSH levels, in 127 (10.5%) euthyroid persons, in 24 (12.5%) individuals with decreased serum TSH levels, and in four (57.1%) subjects with hyperthyroidism (P < 0.01). Logistic regression analysis identified overt hyperthyroidism as an independent risk factor for LVH (odds ratio, 13.65; 95% confidence interval, 2.83-65.75; P < 0.01). There is an association between thyroid function status, cardiac mass, and LVH. Hyperthyroidism is an independent risk factor for LVH.

Endothelial nitric oxide synthase Glu298Asp gene polymorphism, blood pressure and hypertension in a general population sample.

OBJECTIVE: The Glu298Asp (E/D) polymorphism of the endothelial nitric oxide synthase (eNOS) gene has been related to hypertension. Since several studies have produced contradictory results, this issue is still subject to ongoing debate. We investigated the association of the eNOS E298D polymorphism with hypertension and with blood pressure (BP) in a large population-based sample of Caucasian ethnicity. DESIGN: Cross-sectional study in a random sample of the general population. METHODS: The eNOS E298D polymorphism was determined by 5'-exonuclease assay among 4219 participants aged 20-79 years of the Study of Health in Pomerania (SHIP). RESULTS: The percentages of the EE298, ED298 and DD298 genotypes were 49.2, 42.0 and 8.8%, respectively. The D allele frequencies did not differ between the groups of normotensive and hypertensive subjects (29.7 versus 29.9%, P = 0.812). Similarly, no association could be established between E298D genotype and prevalent hypertension, neither for D allele carriership (multivariate odds ratio 0.97, 95% confidence interval 0.83-1.12) nor for DD homozygosity (multivariate odds ratio 1.10, 95% confidence interval 0.84-1.43). Likewise, genotype groups did not differ as to the distribution of systolic (ANCOVA P = 0.917) or diastolic BP values (ANCOVA P = 0.657). Nearly identical results were obtained if the analyses were repeated sex-specifically or if subjects on antihypertensive medication were excluded. CONCLUSION: In a population-based cohort of Caucasians covering a broad age range, the eNOS E298D polymorphism is neither associated with prevalent hypertension nor with systolic or diastolic BP. These results do not support the hypothesis that the E298D polymorphism contributes to the genetic susceptibility to hypertension.

Reference intervals of serum thyroid function tests in a previously iodine-deficient area.

AIM: We undertook the present study to establish reference data for serum thyroid function tests in a previously iodine-deficient area. METHODS: Data from 4298 individuals, 20-79 years of age were available for the present analysis. Thyroid function (thyrotropin [TSH], free triiodothyronine [FT(3)], and free thyroxine [FT(4)]) and serum autoantibodies to thyroperoxidase (anti-TPOAb) were evaluated from blood samples. Thyroid structure and size were measured by ultrasound. RESULTS: A reference population was selected comprising 1488 persons (825 men) by excluding subjects with known thyroid diseases, and with yet unknown thyroid disorders such as goitre, inhomogeneous thyroid pattern, nodules, hypoechogenicity and anti-TPOAb seropositivity. Reference intervals for serum TSH, FT(3), and FT(4) were 0.25-2.12 mIU/L, 3.8-7.0 pmol/L, and 8.3-18.9 pmol/L, respectively. Reference serum TSH levels were not comparable to the reference values that were recently established for the U.S. population and most reference values slightly differed from the reference values provided by the manufacturers. CONCLUSIONS: The reference ranges of thyroid function tests in this formerly iodine-deficient region are distinct from the reference ranges that were established in areas with iodine sufficiency. Creating a reference population in the present setting should include thyroid ultrasound in order to exclude yet undiagnosed thyroid disorders.