Novel mutation in the adiponectin (ADIPOQ) gene is associated with hypoadiponectinaemia in Japanese-Brazilians

P>Objective Adiponectin is an important mediator of insulin sensitivity, encoded by the ADIPOQ gene. Here we describe two Japanese-Brazilian families with hypoadiponectinaemia due to a novel mutation in ADIPOQ. Design and patients In this study, we examined the entire translated regions of adiponectin in Japanese-Brazilians, a population with one of the highest prevalence rates of diabetes worldwide. We screened 200 patients with type 2 diabetes (DM) and 240 age-matched subjects with normal glucose tolerance. Results A novel heterozygous T deletion at position 186 in exon 2 of ADIPOQ, causing a frameshift at codon 62 and leading to a premature termination at codon 168 (p.Gly63ValfsX106), was found in two individuals with diabetes. This mutation was not found in 240 nondiabetic control subjects. In addition, we screened the mutation in an expanded set of 100 nondiabetic subjects from the general Brazilian population, but we found no mutations. In addition, six family members of the probands were identified as mutation-carriers. Individuals who were mutation-carriers had markedly low plasma adiponectin concentrations compared with those without the mutation [DM: 0 center dot 65 (0 center dot 59-1 center dot 34) mu g/ml vs. 5 center dot 30 (3 center dot 10-8 center dot 55) mu g/ml, P < 0 center dot 0001; normal glucose tolerance: 0 center dot 95 (0 center dot 76-1 center dot 48) mu g/ml vs. 8 center dot 50 (5 center dot 52-14 center dot 55) mu g/ml, P = 0 center dot 003]. All individuals carrying the p.Gly63ValfsX106 mutation and older than 30 years were found to be diabetic. Conclusions We describe for the first time a frameshift mutation in exon 2 of the ADIPOQ gene, which modulates adiponectin levels and may contribute to the genetic risk of late-onset diabetes in Japanese-Brazilians.

Dietary fructose, fruits, fruit juices and glucose tolerance status in Japanese-Brazilians

Background and aims: Evidence suggests that fructose and sweetened beverages may be a risk factor for obesity and type 2 diabetes, but the role of sweetened fruit juices in glucose disturbances has been minimally explored. The aim of this study was to examine the association of total fructose, fresh fruit and sweetened fruit juice intake with glucose tolerance homeostasis in Japanese-Brazilians. Methods and results: A total of 475 men and 579 women aged >= 30 years were evaluated in a cross-sectional population-based survey with a standardized protocol including a 2-h oral glucose tolerance test (WHO criteria). Habitual food consumption was obtained using a validated food frequency questionnaire for Japanese-Brazitians. After adjustments for potential confounding variables, the odds ratio (OR; 95%Cl) for impaired glucose tolerance was 2.1 (1.0-4.5; P for trend = 0.05) for the highest as compared to the lowest tertile intake of total fructose and 2.3 (1.1-5.1; P for trend = 0.05) for the highest as compared to the lowest tertile intake of sweetened fruit juices. Conclusion: Our results showed that high intakes of dietary fructose and sweetened fruit juices, but not whole fresh fruits, were associated with impaired glucose tolerance among genetically susceptible individuals. (C) 2008 Elsevier B.V. All rights reserved.

ADRB2 and LEPR Gene Polymorphisms: Synergistic Effects on the Risk of Obesity in Japanese

The objective of the present study was to validate a recently reported synergistic effect between variants located in the leptin receptor (LEPR) gene and in the beta-2 adrenergic receptor (ADRB2) gene on the risk of overweight/obesity. We studied a middle-aged/ elderly sample of 4,193 nondiabetic Japanese subjects stratified according gender (1,911 women and 2,282 men). The LEPR Gln223Arg (rs1137101) variant as well as both ADRB2 Arg16Gly (rs1042713) and Gln27Glu (rs1042714) polymorphisms were analyzed. The primary outcome was the risk of overweight/obesity defined as BMI >= 25 kg/m(2), whereas secondary outcomes included the risk of a BMI >= 27 kg/m(2) and BMI as a continuous variable. None of the studied polymorphisms showed statistically significant individual effects, regardless of the group or phenotype studied. Haplotype analysis also did not disclose any associations of ADRB2 polymorphisms with BMI. However, dimensionality reduction-based models confirmed significant interactions among the investigated variants for BMI as a continuous variable as well as for the risk of obesity defined as BMI >= 27 kg/m(2). All disclosed interactions were found in men only. Our results provide external validation for a male specific ADRB2-LEPR interaction effect on the risk of overweight/obesity, but indicate that effect sizes associated with these interactions may be smaller in the population studied.

O sincretismo de culturas sob a ótica da arquitetura vernácula do imigrante japonês na cidade de Registro, São Paulo

O presente artigo aborda os métodos construtivos empregados pelos imigrantes japoneses que vieram, em 1918, para a cidade de Registro, na região do Vale do Ribeira do Iguape, no estado de São Paulo. A vinda dessa nova frente de imigração foi incentivada pelo Governo do Estado, com o propósito de promover o processo de colonização, bem como de estimular o desenvolvimento econômico do Vale do Ribeira do Iguape por meio da expansão da cultura do café para a região. As características dessa frente de imigração são muito diferenciadas em relação às demais, tendo em vista que os que dela faziam parte chegaram ao Brasil como proprietários de terras e com apoio financeiro e logístico oferecido por uma empresa particular japonesa, responsável por gerenciar o empreendimento. Esses imigrantes, portanto, contaram com auxílio de uma complexa infra-estrutura, cujo objetivo era viabilizar a sua missão de desenvolvimento da região. Mesmo tendo essa particularidade lhes proporcionado a liberdade de recriar sua cultura em solo brasileiro, a realidade do novo habitat forçou-os a reinterpretar seus hábitos culturais ante as novas circunstâncias físicas, econômicas e sociais encontradas. A fim de entender esse processo de adaptação, foi realizado um estudo dos métodos construtivos empregados em suas edificações, baseado nos conhecimentos desses imigrantes sobre sua arquitetura tradicional. Essa análise permitiu examinar o longo processo de sincretismo entre a cultura oriental e o conhecimento construtivo vernáculo dos habitantes do Vale do Ribeira do Iguape.

Consumo alimentar e doença macrovascular em nipo-brasileiros: um estudo transversal

OBJETIVO: Descrever o hábito alimentar de nipo-brasileiros com e sem doença macrovascular (DMV). MÉTODOS: Definiu-se DMV, para 1.165 nipo-brasileiros, a partir de escores atribuídos ao histórico de saúde, eletrocardiograma e valores do índice tornozelo-braquial. Determinou-se o consumo alimentar habitual por meio de Questionário de Frequência do Consumo de Alimentos. RESULTADOS: A porcentagem de casos confirmados com DMV foi de 3,2%, sendo semelhante entre os sexos. Observou-se, de forma estatisticamente significante, maior frequência de indivíduos com DMV (confirmados ou suspeitos) entre aqueles de primeira geração, com idade > 60 anos, tabagistas, com hipertensão arterial, hipertrigliceridemia e diabetes. Nipo-brasileiros com DMV (confirmados ou suspeitos) apresentaram menor perímetro do quadril e maior idade, pressão arterial sistólica, triglicérides, glicemia, consumo de alimentos fonte de ferro e menor fonte de fibras de grãos. Encontrou-se diferença estatisticamente significante apenas para o consumo de gordura saturada (análise bruta: segundo terço versus primeiro terço). CONCLUSÕES: programas de educação nutricional devem ser incentivados neste grupo com alta prevalência de doenças crônicas não transmissíveis.

Reflexão sobre a imigração japonesa no Brasil sob o ângulo da adiposidade corporal

Populações migrantes representam oportunidade para se investigar a contribuição de fatores ambientais na gênese da obesidade e suas comorbidades. Em 1993, o Japanese-Brazilian Diabetes Study Group estudou a prevalência de diabetes e doenças associadas em nipo-brasileiros residentes em Bauru, SP. Utilizando critérios específicos para asiáticos, 22,4% dos nipo-brasileiros foram caracterizados como portadores de excesso de peso nessa primeira fase do estudo. Na segunda fase, em 2000, essa prevalência subiu para 44,2%, e 50,3% apresentavam obesidade central. Essa população também apresentava alta prevalência de diabetes tipo 2, hipertensão e dislipidemia, componentes da síndrome metabólica. O JBDS Group também mostrou a associação entre hábitos ocidentais, especialmente alimentação rica em gordura saturada, e a ocorrência de síndrome metabólica. Em 2005, motivado por esses achados, o JBDS Group iniciou a terceira fase do estudo que constou de programa de intervenção com base em orientação para dieta saudável e prática de atividade física, utilizando recursos factíveis em termos de saúde pública no Brasil. Após um ano de intervenção, o JBDS Group observou diminuição nos parâmetros antropométricos, pressão arterial e níveis de glicemia e colesterol. Tempo de acompanhamento maior é necessário para avaliar a persistência desses benefícios e o impacto deles no risco de desenvolver diabetes e eventos cardiovasculares.

Distúrbios no perfil lipídico são altamente prevalentes em população nipo-brasileira

Alta prevalência de diabetes em população nipo-brasileira de Bauru/SP foi previamente relatada. Visando a complementar a avaliação do risco cardiometabólico, este estudo analisou distúrbios no perfil lipídico de 1.330 nipo-brasileiros (46% homens) > 30 anos. Definiu-se hipercolesterolemia por níveis de colesterol total > 240 mg/dL; hipertrigliceridemia por valores > 150 mg/dL e HDL-colesterol baixo por valores < 40 mg/dL e < 50 mg/dL para homens e mulheres, respectivamente. A prevalência desses distúrbios foi comparada pelo qui-quadrado, estratificando-se por sexos e categorias glicêmicas. As médias dos lipídeos e lipoproteínas foram comparadas entre sexos pelo teste t de Student. A prevalência de hipertrigliceridemia foi de 66,0% (IC95%:63,5 - 68,5%), sendo mais comum em homens e aumentando com a piora da categoria glicêmica; a trigliceridemia média foi 235,7 ± 196,3 mg/dL. A prevalência de hipercolesterolemia foi 24,4% (IC95%:22,1 - 26,7%); HDL-C baixo foi observado em 43,0% (IC95%:39,4 - 46,6%] das mulheres e 17,5% (IC95%:14,5 - 20,5%) dos homens, porém a razão colesterol total/HDL-C foi menor em mulheres (4,23 ± 0,68 vs. 4,40 ± 0,73; p < 0,001). Em nipo-brasileiros, a hipertrigliceridemia é a anormalidade lipídica mais comum, em concordância com a elevada prevalência de diabetes. Os homens apresentaram pior perfil lipídico que as mulheres. Sugere-se que hábitos de vida ocidental possam estar deteriorando a saúde desses indivíduos.

Prevalência de sobrepeso e obesidade em nipo-brasileiros: comparação entre sexos e geração

OBJETIVO: Descrever a prevalência de sobrepeso, obesidade e obesidade abdominal em nipo-brasileiros residentes na cidade de Bauru (SP), Brasil. MÉTODOS: Os dados foram obtidos a partir de um estudo transversal com 1 330 nipo-brasileiros de 1ª e 2ª geração, de ambos os sexos, com idade >30 anos. Os critérios para sobrepeso e obesidade foram índice de massa corporal entre 25-29,9kg/m² e >30kg/m², respectivamente. A obesidade abdominal foi classificada com valores de circunferência da cintura >90cm, para homens, e >80cm para mulheres. Foram calculadas as prevalências de sobrepeso, obesidade e obesidade abdominal por ponto e por intervalo, com 95% de confiança. RESULTADOS: Verificou-se que a prevalência de sobrepeso em nipo-brasileiros foi de 26,1% e 27,9% na primeira geração e de 44,8% e 32,5% na segunda geração, respectivamente, para homens e mulheres. Em relação à obesidade, a prevalência entre homens foi de 3,7% e 12%, e nas mulheres de 6,6% e 9,9% respectivamente na primeira e na segunda geração. Observou-se aumento na prevalência de sobrepeso e obesidade nos homens entre as gerações, apesar de as diferenças não serem estatisticamente significantes. A obesidade abdominal nos homens de primeira e segunda geração foi de 32,1% e 45,3%, e nas mulheres estes valores foram de 49,2% e 48,5%, respectivamente. No período de estudo não foram observados aumentos nas prevalências de sobrepeso e obesidade estatisticamente significantes (p<0,05). CONCLUSÃO: O aumento percentual na prevalência de sobrepeso e obesidade abdominal em nipo-brasileiros pode ser, em parte, explicado pelo processo da ocidentalização, reforçando a necessidade de medidas preventivas, visando a minimizar as conseqüências metabólicas da obesidade nos nipo-brasileiros.

Avaliação da ingestão de alimentos por nipo-brasileiros utilizando análise fatorial

Descreve-se o uso da análise fatorial na avaliação dos hábitos alimentares de nipo-brasileiros. Utilizaram-se dados dietéticos de 1.283 participantes de estudo transversal. A partir de critérios estatísticos e do significado conceitual dos padrões identificados, geraram-se escores que definiram os perfis dietéticos (japonês ou ocidental). Empregou-se o teste t de Student pareado, os modelos de regressão linear e de Poisson para examinar as relações desses escores com, respectivamente, a geração, índice de massa corporal (IMC), perímetro abdominal e a presença de síndrome metabólica. Aqueles de primeira geração, em relação aos de segunda, apresentaram escores maiores para o perfil japonês e menores para o ocidental. O perfil ocidental relacionou-se com o IMC (p = 0,001), perímetro abdominal (p = 0,023) e a síndrome metabólica (p < 0,05). Conclui-se que os escores discriminaram sujeitos que mantêm ou não estilo de vida tradicional japonês e que a incorporação de hábitos ocidentais associou-se a maiores valores de IMC, perímetro abdominal e a presença de síndrome metabólica

The Borg Scale as an Important Tool of Self-Monitoring and Self-Regulation of Exercise Prescription in Heart Failure Patients During Hydrotherapy - A Randomized Blinded Controlled Trial

Background: The Borg Scale may be a useful tool for heart failure patients to self-monitor and self-regulate exercise on land or in water (hydrotherapy) by maintaining the heart rate (HR) between the anaerobic threshold and respiratory compensation point. Methods and Results: Patients performed a cardiopulmonary exercise test to determine their anaerobic threshold/respiratory compensation points. The percentage of the mean HR during the exercise session in relation to the anaerobic threshold HR (%EHR-AT), in relation to the respiratory compensation point (%EHR-RCP), in relation to the peak HR by the exercise test (%EHR-Peak) and in relation to the maximum predicted HR (%EHR-Predicted) was calculated. Next, patients were randomized into the land or water exercise group. One blinded investigator instructed the patients in each group to exercise at a level between ""relatively easy and slightly tiring"". The mean HR throughout the 30-min exercise session was recorded. The %EHR-AT and %EHR-Predicted did not differ between the land and water exercisegroups, but they differed in the %EHR-RCP (95 +/- 7 to 86 +/- 7. P<0.001) and in the %EHR-Peak (85 +/- 8 to 78 +/- 9, P=0.007). Conclusions: Exercise guided by the Borg scale maintains the patient's HR between the anaerobic threshold and respiratory compensation point (ie, in the exercise training zone). (Circ J 2009; 73: 1871-1876)

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.

Frequency of LCT-13910C > T single nucleotide polymorphism associated with adult-type hypolactasia/lactase persistence among Brazilians of different ethnic groups

Background: Adult-type hypolactasia, the physiological decline of lactase some time after weaning, was previously associated with the LCT -13910C>T polymorphism worldwide except in Africa. Lactase non-persistence is the most common phenotype in humans, except in northwestern Europe with its long history of pastoralism and milking. We had previously shown association of LCT -13910C>T polymorphism with adult-type hypolactasia in Brazilians; thus, we assessed its frequency among different Brazilian ethnic groups. Methods: We investigated the ethnicity-related frequency of this polymorphism in 567 Brazilians [mean age, 42.1 +/- 16.8 years; 157 (27.7%) men]; 399 (70.4%) White, 50 (8.8%) Black, 65 (11.5%) Brown, and 53 (9.3%) Japanese-Brazilian. DNA was extracted from leukocytes; LCT -13910C>T polymorphism was analyzed by PCR-restriction fragment length polymorphism. Results: Prevalence of the CC genotype associated with hypolactasia was similar (57%) among White and Brown groups; however, prevalence was higher among Blacks (80%) and those of Japanese descent (100%). Only 2 (4%) Blacks had TT genotype, and 8 (16%) had the CT genotype. Assuming an association between CC genotype and hypolactasia, and CT and TT genotypes with lactase persistence, 356 (62.8%) individuals had hypolactasia and 211 (37.2%) had lactase persistence. The White and Brown groups had the same hypolactasia prevalence (similar to 57%); nevertheless, was 80% among Black individuals and 100% among Japanese-Brazilians (P < 0.01). Conclusion: The lactase persistence allele, LCT -13910T, was found in about 43% of both White and Brown and 20% of the Black Brazilians, but was absent among all Japanese Brazilians studied.

An assessment of population structure in eight breeds of cattle using a whole genome SNP panel

Background: Analyses of population structure and breed diversity have provided insight into the origin and evolution of cattle. Previously, these studies have used a low density of microsatellite markers, however, with the large number of single nucleotide polymorphism markers that are now available, it is possible to perform genome wide population genetic analyses in cattle. In this study, we used a high-density panel of SNP markers to examine population structure and diversity among eight cattle breeds sampled from Bos indicus and Bos taurus. Results: Two thousand six hundred and forty one single nucleotide polymorphisms ( SNPs) spanning all of the bovine autosomal genome were genotyped in Angus, Brahman, Charolais, Dutch Black and White Dairy, Holstein, Japanese Black, Limousin and Nelore cattle. Population structure was examined using the linkage model in the program STRUCTURE and Fst estimates were used to construct a neighbor-joining tree to represent the phylogenetic relationship among these breeds. Conclusion: The whole-genome SNP panel identified several levels of population substructure in the set of examined cattle breeds. The greatest level of genetic differentiation was detected between the Bos taurus and Bos indicus breeds. When the Bos indicus breeds were excluded from the analysis, genetic differences among beef versus dairy and European versus Asian breeds were detected among the Bos taurus breeds. Exploration of the number of SNP loci required to differentiate between breeds showed that for 100 SNP loci, individuals could only be correctly clustered into breeds 50% of the time, thus a large number of SNP markers are required to replace the 30 microsatellite markers that are currently commonly used in genetic diversity studies.

Predictive factors of non-deterioration of glucose tolerance following a 2-year behavioral intervention

Aim: To identify predictive factors associated with non-deterioration of glucose metabolism following a 2-year behavioral intervention in Japanese-Brazilians. Methods: 295 adults (59.7% women) without diabetes completed 2-year intervention program. Characteristics of those who maintained/improved glucose tolerance status (non-progressors) were compared with those who worsened (progressors) after the intervention. In logistic regression analysis, the condition of non-progressor was used as dependent variable. Results: Baseline characteristics of non-progressors (71.7%) and progressors were similar, except for the former being younger and having higher frequency of disturbed glucose tolerance and lower C-reactive protein (CRP). In logistic regression, non-deterioration of glucose metabolism was associated with disturbed glucose tolerance impaired fasting glucose or impaired glucose tolerance - (p < 0.001) and CRP levels <= 0.04 mg/dL (p = 0.01), adjusted for age and anthropometric variables. Changes in anthropometry and physical activity and achievement of weight and dietary goals after intervention were similar in subsets that worsened or not the glucose tolerance status. Conclusion: The whole sample presented a homogeneous behavior during the intervention. Lower CRP levels and diagnosis of glucose intolerance at baseline were predictors of non-deterioration of the glucose metabolism after a relatively simple intervention, independent of body adiposity.

Consequences for the Bovine Embryo of Being Derived from a Spermatozoon Subjected to Post-Ejaculatory Aging and Heat Shock: Development to the Blastocyst Stage and Sex Ratio

The objective was to determine whether aging of sperm caused by incubation at normothermic (38.5 C) or heat shock (40 C) temperatures for 4 h prior to oocyte insemination affects sperm motility, fertilizing ability, competence of the resultant embryo to develop to the blastocyst stage and blastocyst sex ratio. In the first experiment, the percent of sperm that were motile was reduced by aging (P<0.001) and the reduction in motility was greater for sperm at 40 C compared to sperm at 38.5 C (P<0.01). In the second experiment, oocytes were inseminated with aged sperm. A smaller percent of oocytes fertilized with sperm aged at either temperature cleaved by Day 3 after insemination than oocytes fertilized with fresh sperm (P<0.05). There was no effect of sperm aging on the percent of oocytes or cleaved embryos that developed to the blastocyst stage. Aging of sperm before fertilization at 38.5 C reduced the percent of blastocysts that were male (P=0.08). In the third experiment, incubation of sperm at 38.5 C or 40 C for 4 h did not reduce fertilizing ability of sperm as determined by pronuclear formation at 18 h post insemination. In conclusion, aging of sperm reduced cleavage rate and the percent of blastocysts that were males but had no effect on the developmental capacity of the. embryo. The effect of aging on cleavage rate may represent reduced motility and errors occurring after fertilization and pronuclear formation. Aging at a temperature characteristic of maternal hyperthermia had little additional effect except that polyspermy was reduced. Results indicate that embryo competence for development to the blastocyst stage is independent of sperm damage as a result of aging for 4 h at normothermic or hyperthermic temperatures.