Levels and determinants of inflammatory biomarkers in a Swiss population-based sample (CoLaus study)

Objective to assess the levels and determinants of interleukin (IL)-1β, IL-6, tumour necrosis factor (TNF)-α and C-reactive protein (CRP) in a healthy Caucasian population. Methods population sample of 2884 men and 3201 women aged 35 to 75. IL-1β, IL-6 and TNF-α were assessed by a multiplexed particle-based flow cytometric assay and CRP by an immunometric assay. Results Spearman rank correlations between duplicate cytokine measurements (N = 80) ranged between 0.89 and 0.96; intra-class correlation coefficients ranged between 0.94 and 0.97, indicating good reproducibility. Among the 6085 participants, 2289 (37.6%), 451 (7.4%) and 43 (0.7%) had IL-1β, IL-6 and TNF-α levels below detection limits, respectively. Median (interquartile range) for participants with detectable values were 1.17 (0.48–3.90) pg/ml for IL-1β; 1.47 (0.71–3.53) pg/ml for IL-6; 2.89 (1.82–4.53) pg/ml for TNF-α and 1.3 (0.6–2.7) ng/ml for CRP. On multivariate analysis, greater age was the only factor inversely associated with IL-1β levels. Male sex, increased BMI and smoking were associated with greater IL-6 levels, while no relationship was found for age and leisure-time PA. Male sex, greater age, increased BMI and current smoking were associated with greater TNF-α levels, while no relationship was found with leisure-time PA. CRP levels were positively related to age, BMI and smoking, and inversely to male sex and physical activity. Conclusion Population-based levels of several cytokines were established. Increased age and BMI, and to a lesser degree sex and smoking, significantly and differentially impact cytokine levels, while leisure-time physical activity has little effect.

A Statistical Study of the Association of Seven Dental Anomalies in the Brazilian Population

The objective of this study was to show the association patterns among seven types of dental anomalies (second pre-molar agenesis, upper side incisive reduced in size, lower first molar infra-ochlesis, enamel hypoplasia, first molar ectopic eruption, supra numerous teeth and upper canine ectopic eruption) in a population sample without dental treatment ranging in age from 7 to 14. A total of 172 patients were attended and underwent the clinical examination at the Clinica Infantil da Fundacao Educacional de Barretos. Eleven patients from this total were selected according to a first dental anomaly diagnosis and submitted to panoramic radiography. A significant association (p < 0.05) was detected among six pairs of anomalies (second pre-molar agenesis x first pre-molar ectopic eruption; second pre-molar agenesis x lower first molar infra-ochlesis; second pre-molar agenesis x upper side incisive reduced in size; supra numerous teeth x reduced size upper side incisive; first pre-molar ectopic eruption x enamel hypoplasia; lower first molar infra-ochlesis x upper side incisive reduced in size) suggesting a common genetic origin for these conditions. The association was not significant in only one case where there was anomaly sharing by the patients. The existence of an anomaly is clinically relevant for early diagnosis of a possible association and an anomaly can indicate an increased risk of other anomalies.

Derivation and external validation of a simple prediction model for the diagnosis of type 2 Diabetes Mellitus in the Brazilian urban population

A risk score model was developed based in a population of 1,224 individuals from the general population without known diabetes aging 35 years or more from an urban Brazilian population sample in order to select individuals who should be screened in subsequent testing and improve the efficacy of public health assurance. External validation was performed in a second, independent, population from a different city ascertained through a similar epidemiological protocol. The risk score was developed by multiple logistic regression and model performance and cutoff values were derived from a receiver operating characteristic curve. Model`s capacity of predicting fasting blood glucose levels was tested analyzing data from a 5-year follow-up protocol conducted in the general population. Items independently and significantly associated with diabetes were age, BMI and known hypertension. Sensitivity, specificity and proportion of further testing necessary for the best cutoff value were 75.9, 66.9 and 37.2%, respectively. External validation confirmed the model`s adequacy (AUC equal to 0.72). Finally, model score was also capable of predicting fasting blood glucose progression in non-diabetic individuals in a 5-year follow-up period. In conclusion, this simple diabetes risk score was able to identify individuals with an increased likelihood of having diabetes and it can be used to stratify subpopulations in which performing of subsequent tests is necessary and probably cost-effective.

Lack of association between CYP1A1 polymorphism and Parkinson's disease in a Chinese population

Apart from very few families who have a direct cause from genetic mutation, causes of most Parkinson's disease (PD) remain unclear. Many allelic association studies on polymorphism of different candidate genes have been studied. Although these association studies do not imply a causal relationship, it does warrant further studies to elucidate the pathophysiologic significance. CYP1A1 polymorphisms have been reported to be associated with PD in a Japanese population sample. Since CYP1A1 transforms aromatic hydrocarbons into products that may be neurotoxic and perhaps lead to PD, we therefore undertook a study to look at the possible association of CYP1A1 polymorphism and PD in a Chinese population. Contrary to the Japanese result, we did not find any statistically significant difference between the PD group and the control group in our study with a bigger sample size.

Histoplasmin and paracoccidioidin skin reactivity in infantile population of Northern Argentina

In order to estimate ages at which etiological agents of systemic mycoses initiate infection, histoplasmin and paracoccidioidin skin tests were performed in 344 children of both sexes, between 2 and 15 years old. They were selected from a statistically significant population sample Gral. San Martín city (Northeast Argentina). Tests were read 48h after injection and considered positive if a 5 mm on larger induration was present. Circulating antibodies were also evaluated by agar gel immunodiffusion. The overall infection rate for H. capsulatum was 9.2%, belonging to children from 4 to 14 years old, without significant differences among sexes. Five children from 2 to 14 years old were positive to paracoccidioidin (1.6%). None of the children had specific antibodies neither signs of active mycosis. Results show H. capsulatum infection can be found from age 4, while for P. brasiliensis the lower limit was two years old. These findings may contribute to better knowledge on infantile fungal infection in a geographical region where no previous references can be found.

Normal values of echocardiographic measurements. A population-based study

OBJECTIVE: To describe echocardiographic measurements and left ventricular mass in a population sample of healthy adults inhabitants of the urban region of Porto Alegre. METHODS: An analytical, observational, population-based, cross-sectional study was done. Through a multi-stage probability sample, 114 individuals were selected to be submitted to a M-mode and two-dimensional echocardiogram with color Doppler. The analyses were restricted to healthy participants. Echocardiographic measurements were described by mean, standard deviation, 95 percentile and 95% confidence limits. RESULTS: A total of 100 healthy participants, with several characteristics similar to those from the original population, had a complete and reliable echocardiographic examination. The measurements of aorta, left atrium, interventricular septum, left ventricle in systole and diastole, left posterior wall and left ventricular mass, adjusted or not for body surface area or height, were significantly higher in males. The right ventricle size was similar among the genders. Several echocardiographic measurements were within standard normal limits. Interventricular septum, left posterior wall and left ventricular mass, adjusted or not for anthropometric measurements, and aortic dimensions had lower mean and range than the reference limits. CONCLUSION: The means and estimates of distribution for the measurements of interventricular septum, left posterior wall and left ventricular mass found in this survey were lower than those indicated by the international literature and accepted as normal limits.

Frequency of CCR5 Delta-32 Mutation in Human Immunodeficiency Virus (HIV)-seropositive and HIV-exposed Seronegative Individuals and in General Population of Medellin, Colombia

Repeated exposure to human immunodeficiency virus (HIV) does not always result in seroconversion. Modifications in coreceptors for HIV entrance to target cells are one of the factors that block the infection. We studied the frequency of Delta-32 mutation in ccr5 gene in Medellin, Colombia. Two hundred and eighteen individuals distributed in three different groups were analyzed for Delta-32 mutation in ccr5 gene by polymerase chain reaction (PCR): 29 HIV seropositive (SP), 39 exposed seronegative (ESN) and 150 individuals as a general population sample (GPS). The frequency of the Delta-32 mutant allele was 3.8% for ESN, 2.7% for GPS and 1.7% for SP. Only one homozygous mutant genotype (Delta-32/Delta-32) was found among the ESN (2.6%). The heterozygous genotype (ccr5/Delta-32) was found in eight GPS (5.3%), in one SP (3.4%) and in one ESN (2.6%). The differences in the allelic and genotypic frequencies among the three groups were not statistically significant. A comparison between the expected and the observed genotypic frequencies showed that these frequencies were significantly different for the ESN group, which indirectly suggests a protective effect of the mutant genotype (Delta-32/Delta-32). Since this mutant genotype explained the resistance of infection in only one of our ESN persons, different mechanisms of protection must be playing a more important role in this population.

Physical activity assessment using a pedometer and its comparison with a questionnaire in a large population survey.

The aim of this study was to evaluate the use of the pedometer in epidemiologic research on physical activity. Within the framework of a health examination survey in 1988-1989, physical activity was assessed in a representative population sample of 493 men and women aged 25-74 years who were residents of Switzerland. They wore a pedometer for 1 week at work and during leisure time, and the results, converted into steps per day, were compared with answers to a questionnaire. The average number of steps per day decreased from 11,900 to 6,700 and from 9,300 to 7,300 for men and women, respectively, in the youngest to the oldest age groups. For men, categorized according to type of physical activity at work, there was a highly significant difference in the number of steps (p < 0.001), whereas in women the results were associated with leisure-time physical activity (p = 0.003). For both sexes, practicing sports more than once a week was associated with an important increase in steps per day. Analyzing the number of steps according to the day of the week and occupational category produced an unexpected result: Men with a physically active job engaged in more leisure-time physical activity on the weekend. The pedometer proved to be useful in assessing physical activity in a large, free-living population.

Tunisian population data on 10 Y-chromosomal loci.

Alleles and haplotypes frequencies for 10 Y-chromosome STR loci (DYS19, DYS385 I/II, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS438 and DYS439), included in the Y-Plex6 and Y-Plex5 kits were determined for a Tunisian population sample of 100 male individuals.

Objective Sleep Structure and Cardiovascular Risk Factors in the General Population: The HypnoLaus Study.

STUDY OBJECTIVES: To evaluate the association between objective sleep measures and metabolic syndrome (MS), hypertension, diabetes, and obesity. DESIGN: Cross-sectional study. SETTING: General population sample. PARTICIPANTS: There were 2,162 patients (51.2% women, mean age 58.4 ± 11.1). INTERVENTIONS: Patients were evaluated for hypertension, diabetes, overweight/obesity, and MS, and underwent a full polysomnography (PSG). MEASUREMENTS AND RESULTS: PSG measured variables included: total sleep time (TST), percentage and time spent in slow wave sleep (SWS) and in rapid eye movement (REM) sleep, sleep efficiency and arousal index (ArI). In univariate analyses, MS was associated with decreased TST, SWS, REM sleep, and sleep efficiency, and increased ArI. After adjustment for age, sex, smoking, alcohol, physical activity, drugs that affect sleep and depression, the ArI remained significantly higher, but the difference disappeared in patients without significant sleep disordered breathing (SDB). Differences in sleep structure were also found according to the presence or absence of hypertension, diabetes, and overweight/obesity in univariate analysis. However, these differences were attenuated after multivariate adjustment and after excluding subjects with significant SDB. CONCLUSIONS: In this population-based sample we found significant associations between sleep structure and MS, hypertension, diabetes, and obesity. However, these associations were cancelled after multivariate adjustment. We conclude that normal variations in sleep contribute little if any to MS and associated disorders.

Assessment of the COOP charts with and without pictures in a Swiss population.

OBJECTIVES: This study aimed to assess the validity of COOP charts in a general population sample, to examine whether illustrations contribute to instrument validity, and to establish general population norms. METHODS: A general population mail survey was conducted among 20-79 years old residents of the Swiss canton of Vaud. Participants were invited to complete COOP charts, the SF-36 Health Survey; they also provided data on health service use in the previous month. Two thirds of the respondents received standard COOP charts, the rest received charts without illustrations. RESULTS: Overall 1250 persons responded (54%). The presence of illustrations did not affect score distributions, except that the illustrated 'physical fitness' chart drew greater non-response (10 vs. 3%, p < 0.001). Validity tests were similar for illustrated and picture-less charts. Factor analysis yielded two principal components, corresponding to physical and mental health. Six COOP charts showed strong and nearly linear relationships with corresponding SF36 scores (all p < 0.001), demonstrating concurrent validity. Similarly, most COOP charts were associated with the use of medical services in the past month. Only the chart on 'social support' partly deviated from construct validity hypotheses. Population norms revealed a generally lower health status in women and an age-related decline in physical health. CONCLUSIONS: COOP charts can be used to assess the health status of a general population. Their validity is good, with the possible exception of the 'social support' chart. The illustrations do not affect the properties of this instrument.

Consommation d'aliments riches en calcium dans la population adulte de Suisse romande et du Tessin. [Consumption of calcium-rich food in the adult population of French-speaking Switzerland and of Tessin].

Food intake high in calcium content is important in the development of skeleton and the prevention of osteoporosis. From a public health perspective, it is therefore important to know the dietary calcium intake of a population. Two population surveys in the French and Italian parts of Switzerland (MONICA, 1988-1989, and Geneva, 1991), were combined to study nutritional habits related to calcium intake. A random population sample, aged 35 et 65 years, answered to a 24 hour recall questionnaire, either self-administered (MONICA, cantons of Vaud, Fribourg and Tessin, N = 2734) or by phone (canton of Geneva, N = 475). In the 4 cantons, for the previous day, 60% of participants ate dairy products, particularly whole milk and cheese. They drunk 3-4 dl/day of milk. A significant proportion (10%) of french and italian speaking Swiss did not consume any food high in calcium content. In Geneva, the mean daily calcium intake was 656 mg in men and 489 mg in women. In conclusion 1) eating habits related to calcium intake are similar across cantons; 2) women consume dairy products more frequently than men, but in smaller quantities; 3) about 60% of men and 80% of women do not get the daily amount of calcium recommended for the prevention of osteoporosis.

Evidence for chronic low-grade systemic inflammation in individuals with agoraphobia from a population-based prospective study.

BACKGROUND: Anxiety disorders have been linked to an increased risk of incident coronary heart disease in which inflammation plays a key pathogenic role. To date, no studies have looked at the association between proinflammatory markers and agoraphobia. METHODS: In a random Swiss population sample of 2890 persons (35-67 years, 53% women), we diagnosed a total of 124 individuals (4.3%) with agoraphobia using a validated semi-structured psychiatric interview. We also assessed socioeconomic status, traditional cardiovascular risk factors (i.e., body mass index, hypertension, blood glucose levels, total cholesterol/high-density lipoprotein-cholesterol ratio), and health behaviors (i.e., smoking, alcohol consumption, and physical activity), and other major psychiatric diseases (other anxiety disorders, major depressive disorder, drug dependence) which were treated as covariates in linear regression models. Circulating levels of inflammatory markers, statistically controlled for the baseline demographic and health-related measures, were determined at a mean follow-up of 5.5 ± 0.4 years (range 4.7 - 8.5). RESULTS: Individuals with agoraphobia had significantly higher follow-up levels of C-reactive protein (p = 0.007) and tumor-necrosis-factor-α (p = 0.042) as well as lower levels of the cardioprotective marker adiponectin (p = 0.032) than their non-agoraphobic counterparts. Follow-up levels of interleukin (IL)-1β and IL-6 did not significantly differ between the two groups. CONCLUSIONS: Our results suggest an increase in chronic low-grade inflammation in agoraphobia over time. Such a mechanism might link agoraphobia with an increased risk of atherosclerosis and coronary heart disease, and needs to be tested in longitudinal studies.

The association of ACE gene D/I polymorphism with cardiovascular risk factors in a population from Rio de Janeiro

Our aim was to determine the frequencies of the angiotensin-converting enzyme (ACE) gene alleles D and I and any associations to cardiovascular risk factors in a population sample from Rio de Janeiro, Brazil. Eighty-four adults were selected consecutively during a 6-month period from a cohort subgroup of a previous large cross-sectional survey in Rio de Janeiro. Anthropometric data and blood pressure measurements, echocardiogram, albuminuria, glycemia, lipid profile, and ACE genotype and serum enzyme activity were determined. The frequency of the ACE*D and I alleles in the population under study, determined by PCR, was 0.59 and 0.41, respectively, and the frequencies of the DD, DI, and II genotypes were 0.33, 0.51, and 0.16, respectively. No association between hypertension and genotype was detected using the Kruskal-Wallis method. Mean plasma ACE activity (U/mL) in the DD (N = 28), DI (N = 45) and II (N = 13) groups was 43 (in males) and 52 (in females), 37 and 39, and 22 and 27, respectively; mean microalbuminuria (mg/dL) was 1.41 and 1.6, 0.85 and 0.9, and 0.6 and 0.63, respectively; mean HDL cholesterol (mg/dL) was 40 and 43, 37 and 45, and 41 and 49, respectively, and mean glucose (mg/dL) was 93 and 108, 107 and 98, and 85 and 124, respectively. A high level of ACE activity and albuminuria, and a low level of HDL cholesterol and glucose, were found to be associated with the DD genotype. Finally, the II genotype was found to be associated with variables related to glucose intolerance.

Distribution of ABCB1 polymorphisms among Brazilians: impact of population admixture

Introduction: Interethnic admixture is a source of cryptic population structure that may lead to spurious genotype-phenotype associations in pharmacogenomic studies. We studied the impact of population stratification on the distribution of ABCB1 polymorphisms (1236C > T, 2677G > T/A and 3435C > T) among Brazilians, a highly admixed population with Amerindian, European and African ancestral roots. Methods: Individual DNA from 320 healthy adults was genotyped with a panel of ancestry informative markers, and the proportions of African component of ancestry (ACA) were estimated. ABCB1 genotypes were determined by the single base extension/termination method. We describe the association between ABCB1 polymorphisms and ACA by fitting a linear proportional odds logistic regression model to the data. Results: The distribution of the ABCB1 2677G > T/A and 3435C > T, but not the 1236C > T, SNPs displayed a significant trend for decreasing frequency of the T alleles and TT genotypes from White to Intermediate to Black individuals. The same trend was observed in the frequency of the T/nonG/T haplotype at the 1236, 2677 and 3435 loci. When the population sample was proportioned in quartiles, according to the individual ACA estimates, the frequency of the T allele and TT genotype at each locus declined progressively from the lowest (< 0.25 ACA) to the highest (> 0.75 ACA) quartile. Linear proportional odds logistic regression analysis confirmed that the odds of having the T allele at each locus decreases in a continuous manner with the increase of the ACA, throughout the ACA range (0.13-0.94) observed in the overall population sample. A significant association was also detected between the individual ACA estimates and the presence of the T/nonG/T haplotype in the overall population. Conclusion: Self-identification according to the racial/color categories proposed by the Brazilian Census is insufficient to properly control for population stratification in pharmacogenomic studies of ABCB1.