RESUMO
OBJECTIVE: To establish the possible relation between total caries (TC) and caries severity (CS) with the AMY1 gene copy number (AMY1GCN). MATERIALS AND METHODS: This was an observational, cross-sectional, population-based, and association study with 303 participants. Each participant underwent a complete anamnesis and stomatological check-up, and peripheral blood was obtained to extract gDNA. TC and CS were determined as the number of caries at the dental exploration and the number of dental surfaces affected by caries, respectively, and AMY1GCN was determined by qPCR. RESULTS: We found an elevated caries prevalence (92.7%); TC and CS were 8 ± 10 and 10 ± 13 (median ± IR). There were higher TC and CS in those participants with AMY1GCN above the mean value (0.02 and 0.01 p values, respectively). A positive correlation between TC and CS with AMY1GCN (0.11 and 0.125 r values, 0.03 and 0.01 p values, respectively) was found, in addition to an association between TC and CS with AMY1GCN (1.5 and 1.6 OR values, 0.48 and 0.26 p values, respectively). CONCLUSION: TC and CS were positively related to the AMY1GCN. CLINICAL RELEVANCE: Dental caries has a high prevalence and a multifactorial etiology and has been related to a genetic component. Indeed, the salivary enzyme alpha-amylase could play a significant role in caries susceptibility, considering that its codifying gene (AMY1) can show variation in its gene copy number. This can be considered an important factor for the development of caries at a genetic level.
Assuntos
Suscetibilidade à Cárie Dentária , Cárie Dentária , alfa-Amilases Salivares , Cárie Dentária/enzimologia , Cárie Dentária/epidemiologia , Cárie Dentária/genética , Cárie Dentária/patologia , alfa-Amilases Salivares/genética , alfa-Amilases Salivares/metabolismo , Estudos Transversais , Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Gravidade do Paciente , Suscetibilidade à Cárie Dentária/genética , PrevalênciaRESUMO
Worldwide, Mexico is one of the countries with the highest rate of obesity, which is a condition considered the main risk factor for type 2 diabetes. Among the mechanisms that predispose to obesity, the interaction between food intake and genetic components has been little explored. Recently we evidenced a significant association between the copy number (CN) of AMY1A and AMY2A genes, the enzymatic activity of salivary and pancreatic amylase, and the frequency of childhood obesity in Mexico, a particular population due to the high consumption of starch in the diet and the high prevalence of obesity in children and adults. This review aims to find a better understanding of the role of amylase in obesity through a description of the evolution of the CN of its genes, the association of its enzymatic activity with obesity, and the effect of its interaction with starch intake on Mexican children. In addition, it denotes the importance of the experimental perspectives of further investigation regarding the mechanism by which amylase could regulate the abundance of oligosaccharide-fermenting bacteria and producers of short-chain fatty acids and/or branched-chain amino acids that could contribute to the alteration of the physiological processes associated with intestinal inflammation and metabolic deregulation that predispose to the development of obesity.
A nivel mundial, México es uno de los países con la tasa más alta de obesidad, un padecimiento considerado como el principal factor de riesgo de diabetes tipo 2. Dentro de los mecanismos que predisponen a la obesidad, la interacción entre la ingesta alimentaria y el componente genético ha sido poco explorada. Recientemente evidenciamos la asociación del número de copias (NC) de los genes AMY1A y AMY2A, y la actividad enzimática de amilasa salival y pancreática con la frecuencia de obesidad infantil en México, una población que se caracteriza por presentar alto consumo de almidón en la dieta y alta prevalencia de obesidad. La presente revisión busca conseguir un mejor entendimiento del papel de la amilasa en la obesidad por medio de una descripción de la evolución del NC de sus genes, la asociación de su actividad enzimática con la obesidad y el efecto de su interacción con la ingesta de almidón en niños mexicanos. Además, refiere las perspectivas experimentales que permitirían profundizar en la investigación del mecanismo por el cual la amilasa podría regular la abundancia de bacterias fermentadoras de oligosacáridos y productoras de ácidos grasos de cadena corta o aminoácidos de cadena ramificada que podrían contribuir con la alteración de los procesos fisiológicos asociados con la inflamación intestinal y la desregulación metabólica que predispone al desarrollo de obesidad.
Assuntos
Diabetes Mellitus Tipo 2 , Obesidade Infantil , alfa-Amilases Salivares , Humanos , Obesidade Infantil/genética , Amilases/genética , alfa-Amilases Salivares/genética , alfa-Amilases Salivares/metabolismo , Genótipo , Amido/metabolismo , FenótipoRESUMO
BACKGROUND: Mexican children are characterized by a high-starch intake diet and high prevalence of obesity. OBJECTIVES: To investigate the association of AMY1A/AMY2A copy numbers (CNs) and AMY1/AMY2 serum enzymatic activity with childhood obesity in up to 427 and 337 Mexican cases and controls. METHODS: Anthropometric and dietary starch intake data were collected. CN of AMY1A/AMY2A and AMY1/AMY2 serum enzymatic activity were determined using droplet digital PCR (ddPCR) and enzymatic colorimetry, respectively. An individual participant level data meta-analysis of association between AMY1A CNVs and obesity was also performed. RESULTS: A positive association between AMY1A/AMY2A CNs and their corresponding AMY1/AMY2 serum enzyme activity was observed in children with normal weight and obesity. The serum enzyme activity of AMY1 and AMY2 was negatively associated with childhood obesity risk, and the association was restricted to kids eating medium/high amount of starch (Pinteraction = .004). While no association between AMY1A and AMY2A CNs and childhood obesity was observed in our sample, we confirmed a significant association between AMY1A CN and obesity in a meta-analysis of 3100 Mexican children. CONCLUSIONS: Our data suggest that genetically determined salivary and pancreatic amylase activity can increase/decrease the risk of obesity in Mexican children, this effect being blunted by a low-starch diet.
Assuntos
Dosagem de Genes , alfa-Amilases Pancreáticas/genética , Obesidade Infantil/etiologia , alfa-Amilases Salivares/genética , Criança , Feminino , Humanos , Masculino , Metanálise como Assunto , alfa-Amilases Pancreáticas/sangue , Obesidade Infantil/enzimologia , alfa-Amilases Salivares/sangueRESUMO
Genome-wide association studies (GWAS) have identified copy number variants (CNVs) associated with obesity in chromosomal regions 1p31.1, 10q11.22, 11q11, 16p12.3, and recently 1p21.1, which contains the salivary amylase gene (AMY1). Recent evidence suggests this enzyme may influence gut microbiota composition through carbohydrate (mainly starch) degradation. The role of these CNVs in obesity has been scarcely explored in the Latino population, and thus the aim of our study was to evaluate the association of 1p31.1, 10q11.22, 11q11, 16p12.3 and 1p21.1 CNVs with obesity in 921 Mexican children, to replicate significant associations in 920 Mexican adults, and to analyze the association of AMY1 copy number with gut microbiota in 75 children and 45 adults. Of the five CNVs analyzed, 1q11 CNV was significantly associated with obesity in children, but not in adults. Only AMY1 CNV was significantly associated with obesity in both age groups. Moreover, gut microbiota analyses revealed a positive correlation between AMY1 copy number and Prevotella abundance. This genus has enzymes and gene clusters essential for complex polysaccharide degradation and utilization. To our knowledge, this is the first study to analyze the association of these five CNVs in the Mexican population and to report a correlation between AMY1 CN and gut microbiota in humans.
Assuntos
Variações do Número de Cópias de DNA , Microbioma Gastrointestinal/genética , Predisposição Genética para Doença , Obesidade/genética , Prevotella , alfa-Amilases Salivares/genética , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Criança , Feminino , Variação Genética , Estudo de Associação Genômica Ampla , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Obesidade/epidemiologia , Adulto JovemRESUMO
Chagas disease (CD) is a parasitic infection that originated in the Americas and is caused by Trypanosoma cruzi. In the last few years, the disease has spread to countries in North America, Asia and Europe due to the migration of Latin Americans. In the Brazilian Amazon, CD has an endemic transmission, especially in the Rio Negro region, where an occupational hazard was described for piaçaveiros (piassaba gatherers). In the State of Amazonas, the first chagasic infection was reported in 1977, and the first acute CD case was recorded in 1980. After initiatives to integrate acute CD diagnostics with the malaria laboratories network, reports of acute CD cases have increased. Most of these cases are associated with oral transmission by the consumption of contaminated food. Chronic cases have also been diagnosed, mostly in the indeterminate form. These cases were detected by serological surveys in cardiologic outpatient clinics and during blood donor screening. Considering that the control mechanisms adopted in Brazil's classic transmission areas are not fully applicable in the Amazon, it is important to understand the disease behavior in this region, both in the acute and chronic cases. Therefore, the pursuit of control measures for the Amazon region should be a priority given that CD represents a challenge to preserving the way of life of the Amazon's inhabitants.
Assuntos
Animais , Digestão/genética , Cavalos/genética , alfa-Amilases Pancreáticas/genética , alfa-Amilases Salivares/genética , Substituição de Aminoácidos , Sequência de Bases , Biodiversidade , Grão Comestível/química , Carboidratos da Dieta , Variação Genética , Técnicas de Genotipagem , Cavalos/classificação , Itália , Polimorfismo de Nucleotídeo Único , Alinhamento de Sequência , Análise de Sequência de DNARESUMO
AIMS/HYPOTHESIS: Childhood obesity is a major public health problem in Mexico, affecting one in every three children. Genome-wide association studies identified genetic variants associated with childhood obesity, but a large missing heritability remains to be elucidated. We have recently shown a strong association between a highly polymorphic copy number variant encompassing the salivary amylase gene (AMY1 also known as AMY1A) and obesity in European and Asian adults. In the present study, we aimed to evaluate the association between AMY1 copy number and obesity in Mexican children. METHODS: We evaluated the number of AMY1 copies in 597 Mexican children (293 obese children and 304 normal weight controls) through highly sensitive digital PCR. The effect of AMY1 copy number on obesity status was assessed using a logistic regression model adjusted for age and sex. RESULTS: We identified a marked effect of AMY1 copy number on reduced risk of obesity (OR per estimated copy 0.84, with the number of copies ranging from one to 16 in this population; p = 4.25 × 10(-6)). The global association between AMY1 copy number and reduced risk of obesity seemed to be mostly driven by the contribution of the highest AMY1 copy number. Strikingly, all children with >10 AMY1 copies were normal weight controls. CONCLUSIONS/INTERPRETATION: Salivary amylase initiates the digestion of dietary starch, which is highly consumed in Mexico. Our current study suggests putative benefits of high number of AMY1 copies (and related production of salivary amylase) on energy metabolism in Mexican children.
Assuntos
Metabolismo dos Carboidratos/genética , Obesidade/genética , alfa-Amilases Salivares/metabolismo , Índice de Massa Corporal , Criança , Feminino , Predisposição Genética para Doença/genética , Variação Genética , Estudo de Associação Genômica Ampla , Humanos , Modelos Logísticos , Masculino , México/epidemiologia , Obesidade/epidemiologia , Saúde Pública , alfa-Amilases Salivares/genéticaRESUMO
The salivary α-amylase is a calcium-binding enzyme that initiates starch digestion in the oral cavity. The α-amylase genes are located in a cluster on the chromosome that includes salivary amylase genes (AMY1), two pancreatic α-amylase genes (AMY2A and AMY2B) and a related pseudogene. The AMY1 genes show extensive copy number variation which is directly proportional to the salivary α-amylase content in saliva. The α-amylase amount in saliva is also influenced by other factors, such as hydration status, psychosocial stress level, and short-term dietary habits. It has been shown that the average copy number of AMY1 gene is higher in populations that evolved under high-starch diets versus low-starch diets, reflecting an intense positive selection imposed by diet on amylase copy number during evolution. In this context, a number of different aspects can be considered in evaluating the possible impact of copy number variation of the AMY1 gene on nutrition research, such as issues related to human diet gene evolution, action on starch digestion, effect on glycemic response after starch consumption, modulation of the action of α-amylases inhibitors, effect on taste perception and satiety, influence on psychosocial stress and relation to oral health.