Hyperhomocysteinemia is independently associated with albuminuria in the population-based CoLaus study.

Increased serum levels of homocysteine and uric acid have each been associated with cardiovascular risk. We analyzed whether homocysteine and uric acid were associated with glomerular filtration rate (GFR) and albuminuria independently of each other. We also investigated the association of MTHFR polymorphisms related to homocysteine with albuminuria to get further insight into causality. This was a cross-sectional population-based study in Caucasians (n = 5913). Hyperhomocysteinemia was defined as total serum homocysteine ≥ 15 μmol/L. Albuminuria was defined as urinary albumin-to-creatinine ratio > 30 mg/g. Uric acid was associated positively with homocysteine (r = 0.246 in men and r = 0.287 in women, P < 0.001). The prevalence of albuminuria increased across increasing homocysteine categories (from 6.4% to 17.3% in subjects with normal GFR and from 3.5% to 14.5% in those with reduced GFR, P for trend < 0.005). Hyperhomocysteinemia (OR = 2.22, 95% confidence interval: 1.60-3.08, P < 0.001) and elevated serum uric acid (OR = 1.27, 1.08-1.50, per 100 μmol/L, P = 0.004) were significantly associated with albuminuria, independently of hypertension and type 2 diabetes. The 2-fold higher risk of albuminuria associated with hyperhomocysteinemia was similar to the risk associated with hypertension or diabetes. MTHFR alleles related to higher homocysteine were associated with increased risk of albuminuria. In the general adult population, elevated serum homocysteine and uric acid were associated with albuminuria independently of each other and of renal function.

Genome-wide association study of major recurrent depression in the U.K. population.

OBJECTIVE: Studies of major depression in twins and families have shown moderate to high heritability, but extensive molecular studies have failed to identify susceptibility genes convincingly. To detect genetic variants contributing to major depression, the authors performed a genome-wide association study using 1,636 cases of depression ascertained in the U.K. and 1,594 comparison subjects screened negative for psychiatric disorders. METHOD: Cases were collected from 1) a case-control study of recurrent depression (the Depression Case Control [DeCC] study; N=1346), 2) an affected sibling pair linkage study of recurrent depression (probands from the Depression Network [DeNT] study; N=332), and 3) a pharmacogenetic study (the Genome-Based Therapeutic Drugs for Depression [GENDEP] study; N=88). Depression cases and comparison subjects were genotyped at Centre National de Génotypage on the Illumina Human610-Quad BeadChip. After applying stringent quality control criteria for missing genotypes, departure from Hardy-Weinberg equilibrium, and low minor allele frequency, the authors tested for association to depression using logistic regression, correcting for population ancestry. RESULTS: Single nucleotide polymorphisms (SNPs) in BICC1 achieved suggestive evidence for association, which strengthened after imputation of ungenotyped markers, and in analysis of female depression cases. A meta-analysis of U.K. data with previously published results from studies in Munich and Lausanne showed some evidence for association near neuroligin 1 (NLGN1) on chromosome 3, but did not support findings at BICC1. CONCLUSIONS: This study identifies several signals for association worthy of further investigation but, as in previous genome-wide studies, suggests that individual gene contributions to depression are likely to have only minor effects, and very large pooled analyses will be required to identify them.

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.

Use of a combined ex vivo/in vivo population approach for screening of human genes involved in the human immunodeficiency virus type 1 life cycle for variants influencing disease progression.

Humans differ substantially with respect to susceptibility to human immunodeficiency virus type 1 (HIV-1). We evaluated variants of nine host genes participating in the viral life cycle for their role in modulating HIV-1 infection. Alleles were assessed ex vivo for their impact on viral replication in purified CD4 T cells from healthy blood donors (n = 128). Thereafter, candidate alleles were assessed in vivo in a cohort of HIV-1-infected individuals (n = 851) not receiving potent antiretroviral therapy. As a benchmark test, we tested 12 previously reported host genetic variants influencing HIV-1 infection as well as single nucleotide polymorphisms in the nine candidate genes. This led to the proposition of three alleles of PML, TSG101, and PPIA as potentially associated with differences in progression of HIV-1 disease. In a model considering the combined effects of new and previously reported gene variants, we estimated that their effect might be responsible for lengthening or shortening by up to 2.8 years the period from 500 CD4 T cells/mul to <200 CD4 T cells/mul.

Participation de la population au dépistage du cancer du sein : déterminants et enjeux

Cet article présente le résumé de l'atelier consacré au dépistage du cancer du sein organisé dans le cadre de la 70e Assemblée annuelle de la Société suisse de médecine interne qui s'est tenue à Genève du 25 au 27 avril 2002. L'objectif de cet atelier était d'identifier, sur la base des programmes pilotes conduits en Suisse ainsi que dans le Bas-Rhin (France), les modalités d'organisation les mieux adaptées au contexte sanitaire et culturel local afin d'optimiser la participation de la population aux programmes de dépistage du cancer susceptibles d'être mis en oeuvre dans les prochaines années. En effet, une participation élevée constitue, avec l'exigence de qualité, la condition nécessaire pour que ces programmes soient efficaces.

Obesity-related phenotypes are associated to parental longevity in a Swiss population-based study

PURPOSE. Longevity has been attributed to decreased cardiovascular mortality. Subjects with long-lived parents may represent a valuable group to study cardiovascular risk factors (CVRF) associated with longevity, possibly leading to new ways of preventing cardiovascular disease. Purpose: Longevity has been attributed to decreased cardiovascular mortality. Subjects with long-lived parents may represent a valuable group to study cardiovascular risk factors (CVRF) associated with longevity, possibly leading to new ways of preventing cardiovascular disease. Methods: We analyzed data from a population-based sample of 2561 participants (1163 men and 1398 women) aged 55--75 years from the city of Lausanne, Switzerland (CoLaus study). Participants were stratified by the number of parents (0, 1, 2) who survived to 85 years or more. Trend across these strata was assessed using a non-parametric kmean test. The associations of parental age (independent covariate used as a proxy for longevity) with fasting blood glucose, blood pressures, blood lipids, body mass index (BMI), weight, height or liver enzymes (continuous dependent variables) were analyzed using multiple linear regressions. Models were adjusted for age, sex, alcohol consumption, smoking and educational level, and BMI for liver enzymes. Results: For subjects with 0 (N=1298), 1 (N=991) and 2 (N=272) long-lived parents, median BMI (interquartile range) was 25.4 (6.5), 24.9 (6.1) and 23.7 (4.8) kg/m2 in women (P<0.001), and 27.3 (4.8), 27.0 (4.5) and 25.9 (4.9) kg/m2 in men (P=0.04), respectively; median weight was 66.5 (16.1), 65.0 (16.4) and 63.4 (13.7) kg in women (P=0.003), and 81.5 (17.0), 81.4 (16.4) and 80.3 (17.1) kg in men (P=0.36). Median height was 161 (8), 162 (9) and 163 (8) cm in women (P=0.005), and 173 (9), 174 (9) and 174 (11) cm in men (P=0.09). The corresponding medians for AST (Aspartate Aminotransferase) were 31 (13), 29 (11) and 28 (10) U/L (P=0.002), and 28 (17), 27 (14) and 26 (19) U/L for ALT (Alanin Aminotransferase, P=0.053) in men. In multivariable analyses, greater parental longevity was associated with lower BMI, lower weight and taller stature in women (P<0.01) and lower AST in men (P=0.011). No significant associations were observed for the other variables analyzed. Sensitivity analyses restricted to subjects whose parents were dead (N=1844) led to similar results, with even stronger associations of parental longevity with liver enzymes in men. Conclusion: In women, increased parental longevity was associated with smaller BMI, attributable to lower weight and taller stature. In men, the association of increased parental longevity with lower liver enzymes, independently of BMI, suggests that parental longevity may be associated with decreased nonalcoholic fatty liver disease.

A single high dose of oral Vitamin D3 is not enough to correct insufficiency and deficiency in a rheumatologic population

Introduction: Vitamin D plays a major role in bone metabolism and neuromuscular function. Supplementation with vitamin D is effective to reduce the risk of fall and of fracture. However adherence to oral daily vitamin D supplementation is low. Screening and correcting vitamin D insufficiency in a general rheumatologic population could improve both morbidity and quality of life in these patients with chronic painful disorders and at high risk of osteoporosis. After determining the prevalence of vitamin D deficiency in this population, we evaluated if supplementation with a single high dose of oral 25-OH vitamin D3 was sufficient to correct this abnormality. Methods: During one month (November 2009), levels of 25-OH vitamin D were systematically determined in our rheumatology outpatient clinic and classified into three groups: vitamin D deficiency (<10 µg/l), vitamin D insufficiency (10 to 30µg/l) or normal vitamin D (>30 µg/l). Patients with insufficiency or deficiency received respectively a single high dose of 300'000 IU or 600'000 IU oral vitamin D3. In addition, all patients with osteoporosis were prescribed daily supplement of calcium (1g) and vitamin D (800 IU). 25-OH vitamin D levels were reevaluated after 3 months. Results: Vitamin D levels were initially determined in 292 patients (mean age 53, 211 women, 87% Caucasian). 77% had inflammatory rheumatologic disease (IRD), 20% osteoporosis (OP) and 12% degenerative disease (DD). Vitamin D deficiency was present in 20 (6.8%), while 225 (77.1%) had insufficiency. Of the 245 patients with levels <30µg/l, a new determination of vitamin D level was available in 173 (71%) at 3 months (table 1). Conclusion: Vitamin D insufficiency is highly prevalent in our rheumatologic population (84%), and is not adequately corrected by a single high dose of oral vitamin D3 in more than half of the patients with IRD and DD. In patients with OP, despite association of a single high dose with daily oral vitamin D supplementation, 40% of patients are still deficient when reevaluated at 3 months.

Retention half times in the skeleton of plutonium and 90Sr from above-ground nuclear tests: a retrospective study of the Swiss population.

Plutonium and (90)Sr are considered to be among the most radiotoxic nuclides produced by the nuclear fission process. In spite of numerous studies on mammals and humans there is still no general agreement on the retention half time of both radionuclides in the skeleton in the general population. Here we determined plutonium and (90)Sr in human vertebrae in individuals deceased between 1960 and 2004 in Switzerland. Plutonium was measured by sensitive SF-ICP-MS techniques and (90)Sr by radiometric methods. We compared our results to the ones obtained for other environmental compartments to reveal the retention half time of NBT fallout (239)Pu and (90)Sr in trabecular bones of the Swiss population. Results show that plutonium has a retention half time of 40+/-14 years. In contrast (90)Sr has a shorter retention half time of 13.5+/-1.0 years. Moreover (90)Sr retention half time in vertebrae is shown to be linked to the retention half time in food and other environmental compartments. These findings demonstrate that the renewal of the vertebrae through calcium homeostatic control is faster for (90)Sr excretion than for plutonium excretion. The precise determination of the retention half time of plutonium in the skeleton will improve the biokinetic model of plutonium metabolism in humans.

Baseline data of a population-based cohort of patients with diabetes in Switzerland (CoDiab-VD)

QUESTIONS UNDER STUDY: To describe a population-based sample of patients with diabetes and the quality of their care in the canton of Vaud, Switzerland, as a baseline measure for the evaluation of the "Programme cantonal Diabète". METHODS: We conducted a self-administered paper-based questionnaire survey. Non-institutionalised adult (aged ≥18 years) patients with diabetes diagnosed for at least 1 year and residing in the canton of Vaud were recruited by community pharmacies. Women with gestational diabetes, people with obvious cognitive impairment or people not sufficiently fluent in French were excluded. Primary outcomes were recommended processes-of-care and outcomes of care (glycosylated haemoglobin [HbA1c], generic and disease-specific health-related quality of life (HRQoL), overall care score in relation to the Chronic Care Model). Other measures included diabetes education, self-management support and self-efficacy, health status, health behaviour and demographics. RESULTS: A total of 519 patients with diabetes were included. Whereas the mean HbA1c level was 7.3% (n = 177, 95% confidence interval 7.1-7.5), diabetes-specific processes-of-care and influenza vaccination were reported by less than two-thirds of the patients. Physical activity and diet recommendations results mirrored patients' difficulties with their management in daily life and diabetes-specific HRQoL was worst in the dimensions relative to diet (eating and drinking) and sex life. A minority of patients reported ever having participated in diabetes education courses (32.8%). Overall, patients were satisfied with their care and the support they received. CONCLUSIONS: This study provides a broad picture of the experiences of people living with diabetes in the canton of Vaud. It shall guide the development of targeted interventions within the "Programme cantonal Diabète".

The population genetics of clonal and partially clonal diploids.

The consequences of variable rates of clonal reproduction on the population genetics of neutral markers are explored in diploid organisms within a subdivided population (island model). We use both analytical and stochastic simulation approaches. High rates of clonal reproduction will positively affect heterozygosity. As a consequence, nearly twice as many alleles per locus can be maintained and population differentiation estimated as F(ST) value is strongly decreased in purely clonal populations as compared to purely sexual ones. With increasing clonal reproduction, effective population size first slowly increases and then points toward extreme values when the reproductive system tends toward strict clonality. This reflects the fact that polymorphism is protected within individuals due to fixed heterozygosity. Contrarily, genotypic diversity smoothly decreases with increasing rates of clonal reproduction. Asexual populations thus maintain higher genetic diversity at each single locus but a lower number of different genotypes. Mixed clonal/sexual reproduction is nearly indistinguishable from strict sexual reproduction as long as the proportion of clonal reproduction is not strongly predominant for all quantities investigated, except for genotypic diversities (both at individual loci and over multiple loci).

Blood pressure normalization in a large population of hypertensive patients treated with perindopril/indapamide combination: results of the OPTIMAX trial.

OBJECTIVE: To determine if the fixed-dose perindopril/indapamide combination (Per/Ind) normalizes blood pressure (BP) in the same fraction of hypertensive patients when treated in everyday practice or in controlled trials. METHODS: In this prospective trial, 17 938 hypertensive patients were treated with Per 2 mg/Ind 0.625 mg for 3-6 months. In Group 1 Per/Ind was initiated in newly diagnosed patients (n = 7032); in Group 2 Per/Ind replaced previous therapy in patients already treated but having either their BP still uncontrolled or experiencing side-effects (n = 7423); in Group 3 Per/Ind was added to previous treatment in patients with persistently high BP (n = 3483). BP was considered normalized when &lt; or = 140/90 mm Hg. A multivariate analysis for predictors of BP normalization was performed. RESULTS: Subjects were on average 62 years old and had a baseline BP of 162.3/93.6 mm Hg. After treatment with Per/Ind, BP normalization was reached in 69.6% of patients in the Initiation group, 67.5% in the Replacement Group, and 67.4% in the Add-on Group (where patients were more frequently at risk, diabetic, or with target organ damage). Mean decreases in systolic BP of 22.8 mm Hg and in diastolic BP of 12.4 mm Hg were recorded. CONCLUSIONS: This trial was established to reflect everyday clinical practice, and a treatment strategy based on the Per/Ind combination, administered as initial, replacement, or add-on therapy, led to normalization rates that were superior to those observed in Europe in routine practice. These results support recent hypertension guidelines which encourage the use of combination therapy in the management of arterial hypertension.