TCF7L2 variant genotypes and type 2 diabetes risk in Brazil: significant association, but not a significant tool for risk stratification in the general population

Background: Genetic polymorphisms of the TCF7L2 gene are strongly associated with large increments in type 2 diabetes risk in different populations worldwide. In this study, we aimed to confirm the effect of the TCF7L2 polymorphism rs7903146 on diabetes risk in a Brazilian population and to assess the use of this genetic marker in improving diabetes risk prediction in the general population. Methods: We genotyped the single nucleotide polymorphisms (SNP) rs7903146 of the TCF7L2 gene in 560 patients with known coronary disease enrolled in the MASS II (Medicine, Angioplasty, or Surgery Study) Trial and in 1,449 residents of Vitoria, in Southeast Brazil. The associations of this gene variant to diabetes risk and metabolic characteristics in these two different populations were analyzed. To access the potential benefit of using this marker for diabetes risk prediction in the general population we analyzed the impact of this genetic variant on a validated diabetes risk prediction tool based on clinical characteristics developed for the Brazilian general population. Results: SNP rs7903146 of the TCF7L2 gene was significantly associated with type 2 diabetes in the MASS-II population (OR = 1.57 per T allele, p = 0.0032), confirming, in the Brazilian population, previous reports of the literature. Addition of this polymorphism to an established clinical risk prediction score did not increased model accuracy (both area under ROC curve equal to 0.776). Conclusion: TCF7L2 rs7903146 T allele is associated with a 1.57 increased risk for type 2 diabetes in a Brazilian cohort of patients with known coronary heart disease. However, the inclusion of this polymorphism in a risk prediction tool developed for the general population resulted in no improvement of performance. This is the first study, to our knowledge, that has confirmed this recent association in a South American population and adds to the great consistency of this finding in studies around the world. Finally, confirming the biological association of a genetic marker does not guarantee improvement on already established screening tools based solely on demographic variables.

CYP2C19 and ABCB1 gene polymorphisms are differently distributed according to ethnicity in the Brazilian general population

Background: Recent studies have reported the clinical importance of CYP2C19 and ABCB1 polymorphisms in an individualized approach to clopidogrel treatment. The aims of this study were to evaluate the frequencies of CYP2C19 and ABCB1 polymorphisms and to identify the clopidogrel-predicted metabolic phenotypes according to ethnic groups in a sample of individuals representative of a highly admixtured population. Methods: One hundred and eighty-three Amerindians and 1,029 subjects of the general population of 4 regions of the country were included. Genotypes for the ABCB1c.C3435T (rs1045642), CYP2C19*2 (rs4244285), CYP2C19*3 (rs4986893), CYP2C19*4 (rs28399504), CYP2C19*5 (rs56337013), and CYP2C19*17 (rs12248560) polymorphisms were detected by polymerase chain reaction followed by high resolution melting analysis. The CYP2C19*3, CYP2C19*4 and CYP2C19*5 variants were genotyped in a subsample of subjects (300 samples randomly selected). Results: The CYP2C19*3 and CYP2C19*5 variant alleles were not detected and the CYP2C19*4 variant allele presented a frequency of 0.3%. The allelic frequencies for the ABCB1c.C3435T, CYP2C19*2 and CYP2C19*17 polymorphisms were differently distributed according to ethnicity: Amerindian (51.4%, 10.4%, 15.8%); Caucasian descent (43.2%, 16.9%, 18.0%); Mulatto (35.9%, 16.5%, 21.3%); and African descent (32.8%, 20.2%, 26.3%) individuals, respectively. As a result, self-referred ethnicity was able to predict significantly different clopidogrel-predicted metabolic phenotypes prevalence even for a highly admixtured population. Conclusion: Our findings indicate the existence of inter-ethnic differences in the ABCB1 and CYP2C19 variant allele frequencies in the Brazilian general population plus Amerindians. This information could help in stratifying individuals from this population regarding clopidogrel-predicted metabolic phenotypes and design more cost-effective programs towards individualization of clopidogrel therapy.

The relationship between cannabis use and other substance use in the general population

This study examined if (1) there is an association in the general population between cannabis use, DSM-IV abuse and dependence, and other substance use and DSM-IV substance abuse/dependence; (2) if so, is it explained by demographic characteristics or levels of neuroticism? It used data from the Australian National Survey of Mental Health and Well-Being (NSMHWB), a stratified, multistage probability sample of 10641 adults, representative of the general population. DSM-IV diagnoses of substance abuse and dependence were derived using the Composite International Diagnostic Interview (CIDI). There was a strong bivariate association between involvement with cannabis use in the past 12 months and other substance use, abuse and dependence. In particular, cannabis abuse and dependence were highly associated with increased risks of other substance dependence. These associations remained after including other variables in multiple regression. Cannabis use without disorder was strongly related to other drug use, an association that was not explained by other variables considered here. The high likelihood of other substance use and substance use disorders needs to be considered among persons seeking treatment for cannabis use problems. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

APOE polymorphism is associated with lipid profile, but not with arterial stiffness in the general population

Background: Cardiovascular diseases (CVD) are the main cause of death and disability in developed countries. In most cases, the progress of CVD is influenced by environmental factors and multifactorial inheritance. The purpose of this study was to investigate the association between APOE genotypes, cardiovascular risk factors, and a noninvasive measure of arterial stiffness in the Brazilian population. Methods: A total of 1493 urban Brazilian individuals were randomly selected from the general population of the Vitoria City Metropolitan area. Genetic analysis of the APOE polymorphism was conducted by PCR-RFLP and pulse wave velocity analyzed with a noninvasive automatic device. Results: Age, gender, body mass index, triglycerides, creatinine, uric acid, blood glucose, blood pressure phenotypes were no different between epsilon 2, epsilon 3 and epsilon 4 alleles. The epsilon 4 allele was associated with higher total-cholesterol (p < 0.001), LDL-C (p < 0.001), total-cholesterol/HDL-C ratio (p < 0.001), LDL/HDL-C ratio (p < 0.001), lower HDL-C values (p < 0.001) and higher risk to obesity (OR = 1.358, 95% CI = 1.019-1.811) and hyperuricemia (OR = 1.748, 95% CI = 1.170-2.611). Nevertheless, pulse wave velocity (p = 0.66) measures were no different between genotypes. The significant association between APOE genotypes and lipid levels persisted after a 5-year follow-up interval, but no interaction between time and genotype was observed for lipids longitudinal behavior. Conclusion: The epsilon 4 allele of the APOE gene is associated with a worse lipid profile in the Brazilian urban population. In our relatively young sample, the observed effect of APOE genotype on lipid levels was not translated into significant effects in arterial wall stiffness.

Screening for serious mental illness in the general population with the K6 screening scale: results from the WHO World Mental Health (WMH) survey initiative

Data are reported on the background and performance of the K6 screening scale for serious mental illness (SMI) in the World Health Organization (WHO) World Mental Health (WMH) surveys. The K6 is a six-item scale developed to provide a brief valid screen for Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) SMI based on the criteria in the US ADAMHA Reorganization Act. Although methodological studies have documented good K6 validity in a number of countries, optimal scoring rules have never been proposed. Such rules are presented here based on analysis of K6 data in nationally or regionally representative WMH surveys in 14 countries (combined N = 41,770 respondents). Twelve-month prevalence of DSM-IV SMI was assessed with the fully-structured WHO Composite International Diagnostic Interview. Nested logistic regression analysis was used to generate estimates of the predicted probability of SMI for each respondent from K6 scores, taking into consideration the possibility of variable concordance as a function of respondent age, gender, education, and country. Concordance, assessed by calculating the area under the receiver operating characteristic curve, was generally substantial (median 0.83; range 0.76-0.89; inter-quartile range 0.81-0.85). Based on this result, optimal scaling rules are presented for use by investigators working with the K6 scale in the countries studied. Copyright (c) 2010 John Wiley & Sons, Ltd.

Evidence for a QTL on chromosome 19 influencing LDL cholesterol levels in the general population

The genetic basis of cardiovascular disease (CVD) with its complex etiology is still largely elusive. Plasma levels of lipids and apolipoproteins are among the major quantitative risk factors for CVD and are well-established intermediate traits that may be more accessible to genetic dissection than clinical CVD end points. Chromosome 19 harbors multiple genes that have been suggested to play a role in lipid metabolism and previous studies indicated the presence of a quantitative trait locus (QTL) for cholesterol levels in genetic isolates. To establish the relevance of genetic variation at chromosome 19 for plasma levels of lipids and apolipoproteins in the general, out-bred Caucasian population, we performed a linkage study in four independent samples, including adolescent Dutch twins and adult Dutch, Swedish and Australian twins totaling 493 dizygotic twin pairs. The average spacing of short-tandem-repeat markers was 6 - 8 cM. In the three adult twin samples, we found consistent evidence for linkage of chromosome 19 with LDL cholesterol levels ( maximum LOD scores of 4.5, 1.7 and 2.1 in the Dutch, Swedish and Australian sample, respectively); no indication for linkage was observed in the adolescent Dutch twin sample. The QTL effects in the three adult samples were not significantly different and a simultaneous analysis of the samples increased the maximum LOD score to 5.7 at 60 cM pter. Bivariate analyses indicated that the putative LDL-C QTL also contributed to the variance in ApoB levels, consistent with the high genetic correlation between these phenotypes. Our study provides strong evidence for the presence of a QTL on chromosome 19 with a major effect on LDL-C plasma levels in outbred Caucasian populations.

Paranoia in the General Population : a revised version of the General Paranoia Scale for Adults

Background: Paranoid ideation has been regarded as a cognitive and a social process used as a defence against perceived threats. According to this perspective, paranoid ideation can be understood as a process extending across the normal-pathological continuum. Methods: In order to refine the construct of paranoid ideation and to validate a measure of paranoia, 906 Portuguese participants from the general population and 91 patients were administered the General Paranoia Scale (GPS), and two conceptual models (one - and tridimensional) were compared through confirmatory factor analysis (CFA). Results: Results from the CFA of the GPS confirmed a different model than the one-dimensional model proposed by Fenigstein and Vanable, which com-prised three dimensions (mistrust thoughts, persecutory ideas, and self-deprecation). This alternative model presented a better fit and increased sensitivity when compared with the one-dimensional model. Further data analysis of the scale revealed that the GPS is an adequate assessment tool for adults, with good psychometric characteristics and high internal consistency. Conclusion: The model proposed in the current work leads to further refinements and enrichment of the construct of paranoia in different populations, allowing the assessment of three dimensions of paranoia and the risk of clinical paranoia in a single measure for the general population.

Paranoia in the General Population : a revised version of the General Paranoia Scale for adolescents

The aim of the current study was to validate the General Paranoia Scale for Portuguese Adolescents population (GPS-A). This scale assesses the paranoid ideation in non-clinical population. Results from a confirmatory factor analysis of the scale on 1218 youths confirmed an alternative model to the one-dimensional model proposed by Fenigstein and Vanable (1992) comprising three different dimensions (Mistrust thoughts, persecutory ideas and depreciation). This alternative model presented a good fit: χ2 (162)= 727.200, p = .000; CFI = .925; RMSEA = .054, P(rmsea ≤0.05) = .000; PCFI = .788; AIC = 863.200. All items presented adequate factor loadings (λij ≥0.5) and individual reliability ((λij)2 ≥0.25). Further data analysis on the scale revealed that the GPS-A is an adequate assessment tool for adolescents, with good psychometric characteristics and high internal consistency.

Frequency of human leukocyte antigen (hla) in patients with malaria and in the general population of Humaitá county, Amazonas state, Brazil

In August 1983,85 inhabitants of the municipality of Humaitá, Amazonas State, Brazil were studied to determine the prevalence of antigens to HLA-A, -B, -C and DR. Thirty-eight were sick with malaria due to Plasmodium falciparum. All subjects were examined for splenomegaly, blood parasitaemia and antibodies to malaria. They constituted three groups: 1) 25 subjects native to the Amazon region who had never had malaria; 2) 38 Amazonian subjects who had malaria in the past or currently had an infection; 3) 22 patients with malaria who had acquired the infection in the Amazon Region but came from other regions of Brazil. Blood was taken from each person, the lymphocytes were separated and typed by the test of microlymphocytotoxicity. There was a high frequency of antigens that could not be identified in the groups studied which suggests the existence of a homozygote or phenotype not identified in the population. There was a high frequency of the phenotype Ag(W24) (44.7%) in group 2 when compared with group 1 (32%) or group 3 (9%). Also the individuals in group 2 showed an elevated frequency of antigen DR(4)80%) when compared with group 1 (36.6%) or group 3 (16.6%). These observations suggest the possibility of a genetic susceptibility to malaria among Amazonian residents and indicate a necessity for more extensive studies of the frequency of HLA antigens among inhabitants of this endemic malarial zone.

Leprosy in Buriticupu, state of Maranhão: active search in the general population

INTRODUCTION: This study was developed to evaluate the situation of leprosy in the general population of the municipality of Buriticupu, State of Maranhão, Brazil. METHODS: We used the method of active search to identify new cases from 2008 to 2010. Bacilloscopy of intradermal scrapings was performed in all patients with skin lesions compatible with leprosy, and histopathological examination in those who had doubts on the definition of the clinical form. RESULTS: The study included 19,104 individuals, with 42 patients diagnosed with leprosy after clinical examination, representing a detection rate of 219.84 per 100,000 inhabitants. The predominant clinical presentation was tuberculoid with 24 (57.1%) cases, followed by borderline with 11, indeterminate with four, and lepromatous with three cases. The study also allowed the identification of 81 patients with a history of leprosy and other skin diseases, such as pityriasis versicolor, dermatophytosis, scabies, vitiligo, and skin carcinoma. The binomial test showed that the proportion of cases in the headquarters was significantly higher than that in the villages (p = 0.04), and the generalized exact test showed that there was no association between age and clinical form (p = 0.438) and between age and gender (p = 0.083). CONCLUSIONS: The elevated detection rate defines the city as hyperendemic for leprosy; the active search for cases, as well as the organization of health services, is an important method for disease control.

Rifapentine for latent tuberculosis infection treatment in the general population and human immunodeficiency virus-positive patients: summary of evidence

AbstractLatent tuberculosis infection (LTBI) and human immunodeficiency virus (HIV)-coinfection are challenges in the control of tuberculosis transmission. We aimed to assess and summarize evidence available in the literature regarding the treatment of LTBI in both the general and HIV-positive population, in order to support decision making by the Brazilian Tuberculosis Control Program for LTBI chemoprophylaxis. We searched MEDLINE, Cochrane Library, Centre for Reviews and Dissemination, Embase, LILACS, SciELO, Trip database, National Guideline Clearinghouse, and the Brazilian Theses Repository to identify systematic reviews, randomized clinical trials, clinical guidelines, evidence-based synopses, reports of health technology assessment agencies, and theses that investigated rifapentine and isoniazid combination compared to isoniazid monotherapy. We assessed the quality of evidence from randomized clinical trials using the Jadad Scale and recommendations from other evidence sources using the Grading of Recommendations, Assessment, Development, and Evaluations approach. The available evidence suggests that there are no differences between rifapentine + isoniazid short-course treatment and the standard 6-month isoniazid therapy in reducing active tuberculosis incidence or death. Adherence was better with directly observed rifapentine therapy compared to self-administered isoniazid. The quality of evidence obtained was moderate, and on the basis of this evidence, rifapentine is recommended by one guideline. Available evidence assessment considering the perspective of higher adherence rates, lower costs, and local peculiarity context might support rifapentine use for LTBI in the general or HIV-positive populations. Since novel trials are ongoing, further studies should include patients on antiretroviral therapy.

Prevalence and characteristics of periodic leg movements during sleep in the general population : the Hypnolaus study

Objective: The aim of this study was to describe the prevalence and characteristics of periodic legs movements of sleep (PLMS) in theadult general population. Methods: Data from 2162 subjects (51.2% women, mean SD age:58, 11 years, range: 40.5-84.4 years) participating in a population-based cohort study (HypnoLaus, Lausanne, Switzerland) wascollected. They completed a series of sleep related questionnaires and underwent polysomnographic recordings at home. PLMS index(PLMSI) was determined according to AASM 2007 criteria. APLMSI>15/h was considered to be of potential clinical significance. Conclusions: PLMS are highly prevalent in the general population. Age, male gender and RLS are independent predictors of a PLMSIhigher than 15/h. Further studies are needed to evaluate the clinical impact of PLMS.