RESUMO
INTRODUCTION: Recent studies have implicated acetyl-L-carnitine as well as other acylcarnitines in depression. To our knowledge, no untargeted metabolomics studies have been conducted among US mainland Puerto Ricans. OBJECTIVES: We conducted untargeted metabolomic profiling on plasma from 736 participants of the Boston Puerto Rican Health Study. METHODS: Using Weighted Gene Co-expression Network Analysis, we identified metabolite modules associated with depressive symptomatology, assessed via the Center for Epidemiologic Studies Depression scale. We identified metabolites contributing to these modules and assessed the relationship between these metabolites and depressive symptomatology. RESULTS: 621 annotated metabolites clustered into eight metabolite modules, of which one, the acylcarnitine module, was significantly inversely associated with depressive symptomatology (ß = - 27.7 (95% CI (- 54.5-0.8); p = 0.043). Several metabolite hub features in the acylcarnitine module were significantly associated with depressive symptomatology, after correction for multiple comparisons. CONCLUSIONS: In this untargeted plasma metabolomics study among mainland Puerto Rican older adults, acylcarnitines, as a metabolite module were inversely associated with depressive symptomatology.
Assuntos
Carnitina , Depressão , Metabolômica , Humanos , Carnitina/análogos & derivados , Carnitina/sangue , Carnitina/metabolismo , Feminino , Masculino , Depressão/sangue , Depressão/metabolismo , Metabolômica/métodos , Pessoa de Meia-Idade , Idoso , Porto Rico , Estudos de Coortes , Hispânico ou Latino , Boston/epidemiologiaRESUMO
BACKGROUND AND AIM: Circulating amino acids are modified by sex, body mass index (BMI) and insulin resistance (IR). However, whether the presence of genetic variants in branched-chain amino acid (BCAA) catabolic enzymes modifies circulating amino acids is still unknown. Thus, we determined the frequency of two genetic variants, one in the branched-chain aminotransferase 2 (BCAT2) gene (rs11548193), and one in the branched-chain ketoacid dehydrogenase (BCKDH) gene (rs45500792), and elucidated their impact on circulating amino acid levels together with clinical, anthropometric and biochemical parameters. METHODS AND RESULTS: We performed a cross-sectional comparative study in which we recruited 1612 young adults (749 women and 863 men) aged 19.7 ± 2.1 years and with a BMI of 24.9 ± 4.7 kg/m2. Participants underwent clinical evaluation and provided blood samples for DNA extraction and biochemical analysis. The single nucleotide polymorphisms (SNPs) were determined by allelic discrimination using real-time polymerase chain reaction (PCR). The frequencies of the less common alleles were 15.2 % for BCAT2 and 9.83 % for BCKDH. The subjects with either the BCAT2 or BCKDH SNPs displayed no differences in the evaluated parameters compared with subjects homozygotes for the most common allele at each SNP. However, subjects with both SNPs had higher body weight, BMI, blood pressure, glucose, and circulating levels of aspartate, isoleucine, methionine, and proline than the subjects homozygotes for the most common allele (P < 0.05, One-way ANOVA). CONCLUSION: Our findings suggest that the joint presence of both the BCAT2 rs11548193 and BCKDH rs45500792 SNPs induces metabolic alterations that are not observed in subjects without either SNP.
Assuntos
3-Metil-2-Oxobutanoato Desidrogenase (Lipoamida)/genética , Aminoácidos/sangue , Antígenos de Histocompatibilidade Menor/genética , Polimorfismo de Nucleotídeo Único , Proteínas da Gravidez/genética , Transaminases/genética , 3-Metil-2-Oxobutanoato Desidrogenase (Lipoamida)/metabolismo , Adolescente , Fatores Etários , Biomarcadores/sangue , Glicemia/análise , Pressão Sanguínea , Índice de Massa Corporal , Estudos Transversais , Feminino , Frequência do Gene , Estudos de Associação Genética , Homozigoto , Humanos , Masculino , México , Antígenos de Histocompatibilidade Menor/metabolismo , Fenótipo , Proteínas da Gravidez/metabolismo , Transaminases/metabolismo , Adulto JovemRESUMO
Cardiometabolic risk involves environmental and genetic factors. We aimed to investigate the relationship between plasma fatty acids and single nucleotide polymorphisms (SNPs), located in elongase and desaturases genes, and cardiometabolic parameters in a cross-sectional population-based survey. A sample of 226 adults who participated in the Health Survey of Sao Paulo, Brazil, was selected. Clinical and anthropometric variables, plasma lipoprotein, and fatty acid were evaluated. We hypothesized that differences in SNPs could lead to changes in plasma long-chain polyunsaturated fatty acids. We analyzed the relationship between SNPs in FADS1 (rs174546) and ELOVL2 (rs953413) genes, plasma fatty acid profiles, and cardiometabolic-related phenotypes using multiple linear regression, which was adjusted for confounders. Plasma high-density lipoprotein cholesterol and low-density lipoprotein cholesterol levels were significantly lower in carriers of the T allele for the FADS1 SNP. Plasma oleic acid levels were statistically higher in individuals with CT/TT genotypes in the FADS1 and AG/GG genotypes in the ELOVL2 SNPs in comparison to the CC and AA genotypes, respectively. Higher levels of linoleic and linolenic acid were found for T-allele carriers of FADS1 SNP. The estimated activity of the stearoyl CoA desaturase enzyme (SDC_18) was higher in the CT/TT genotypes (FADS1). Delta-5 desaturase estimated activity was statistically lower in the presence of the minor FADS1 allele. The estimated activity of the enzyme delta-6 desaturase was statistically lower for FADS1 CT and TT genotypes. SNPs in FADS1 and ELOVL2 genes showed protective associations for lipid metabolism and could be markers of lower cardiometabolic risk.
Assuntos
Ácidos Graxos Dessaturases/genética , Elongases de Ácidos Graxos/genética , Metabolismo dos Lipídeos , Adulto , Brasil , Fatores de Risco Cardiometabólico , Colesterol/sangue , Estudos Transversais , Dessaturase de Ácido Graxo Delta-5 , Ácidos Graxos Dessaturases/metabolismo , Ácidos Graxos/sangue , Ácidos Graxos Insaturados/metabolismo , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Estearoil-CoA Dessaturase/metabolismo , Adulto JovemRESUMO
BACKGROUND: Dietary intervention (DI) is a primary strategy to attenuate some of the metabolic abnormalities associated with metabolic syndrome (MetS), including low HDL cholesterol. There is no biomarker that can identify individuals who respond to DI by increasing HDL cholesterol. OBJECTIVE: The aim of this study was to assess the predictive power of a genetic predisposition score (GPS) in Mexican adults with MetS to identify HDL cholesterol responders to DI. METHODS: This study followed a prospective cohort design. Sixty-seven Mexican adults aged 20-60 y (21% men) with BMI ≥25 and ≤39.9 kg/m², who had at least 3 of 5 positive criteria for MetS, were included. Participants consumed a low saturated fat diet for 2.5 mo (<7% energy as saturated fat, <200 mg of cholesterol/d) and reduced their usual diet by â¼440 kcal/d, a reduction in total energy intake of about 25%. Anthropometry and serum biochemical markers, including HDL cholesterol, were measured before and after DI. A multilocus GPS was constructed using previously reported genetic variants associated with response to diet in subjects with MetS. GPS values, designed to predict the response of HDL cholesterol to the DI, were computed for each individual as the sum of the number of effect alleles across 14 SNPs. RESULTS: Individuals were dichotomized as high and low GPS according to median GPS (-2.12) and we observed a difference in HDL cholesterol changes on DI of +3 mg/dL (6.3%) in subjects with low GPS, whereas those with high GPS had HDL cholesterol decreases of -3 mg/dL (-7.9%) (P = 0.04). CONCLUSIONS: Individuals with low GPS showed greater increases in their HDL cholesterol than those with high GPS. Therefore, the GPS can be useful for predicting the HDL cholesterol response to diet.
Assuntos
HDL-Colesterol/sangue , Síndrome Metabólica/dietoterapia , Adulto , Feminino , Humanos , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/genética , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
Population admixture plays a role in the risk of chronic conditions that are related to body composition; however, our understanding of these associations in Puerto Ricans, a population characterized by multiple ancestries, is limited. This study investigated the relationship between genetic admixture and body composition in 652 Puerto Ricans from the Boston Puerto Rican Osteoporosis Study. Genetic ancestry was estimated from 100 ancestry-informative markers. Body composition measures were obtained from dual-energy X-ray absorptiometry. Multivariable linear regression analyses examined associations between bone mineral density (BMD) of the hip and lumbar spine and percent fat mass and lean mass with genetic admixture. In Puerto Ricans living on the US mainland, European ancestry was associated with lower BMD at the trochanter (P = 0.039) and femoral neck (P = 0.01), and Native American ancestry was associated with lower BMD of the trochanter (P = 0.04). African ancestry was associated with a higher BMD at the trochanter (P = 0.004) and femoral neck (P = 0.001). Ancestry was not associated with percent fat mass or lean mass or waist circumference. Our findings are consistent with existing research demonstrating inverse associations between European and Native American ancestries and BMD and positive relationships between African ancestry and BMD. This work contributes to our understanding of the high prevalence of chronic disease experienced by this population and has implications for other ethnic minority groups, particularly those with multiple ancestries. Future research should consider interactions between ancestry and environmental factors, as this may provide individualized approaches for disease prevention.
Assuntos
Composição Corporal/genética , Osteoporose/genética , Absorciometria de Fóton , Adiposidade/genética , Adulto , Densidade Óssea/genética , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/fisiologia , Boston , Feminino , Estudos de Associação Genética , Hispânico ou Latino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/epidemiologia , Porto Rico , Circunferência da Cintura/genética , População Branca/genéticaRESUMO
BACKGROUND: Omega-3 (n-3) fatty acid (FA) consumption is thought to improve depressive symptoms. However, current evidence is limited, and whether this association exists among Puerto Ricans, a population burdened by depression, remains uncertain. OBJECTIVES: We examined the association between ω-3 FA biomarkers and depressive symptoms as well as the potential influence of oxidative stress. METHODS: Baseline and longitudinal analyses were conducted in the Boston Puerto Rican Health Study (n= 787; participants aged 57 ± 0.52 y, 73% women). Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentration, a measure of oxidative stress, and erythrocyte FA composition were collected at baseline. We calculated the omega-3 index as the sum of eicosapentaenoic and docosahexaenoic acids, expressed as a percentage of total FAs. Baseline and 2-y depressive symptoms were characterized by using the Center for Epidemiological Studies-Depression Scale (CES-D). Statistical analyses included linear and logistic regression. RESULTS: Urinary 8-OHdG concentration tended to modify the relation between the erythrocyte omega-3 index and baseline CES-D score (P-interaction = 0.10). In stratified analyses, the omega-3 index was inversely associated with CES-D score (ß = -1.74, SE = 0.88;P= 0.02) among those in the top quartile of 8-OHdG concentration but not among those in the lower quartiles. The relation between the omega-3 index and CES-D at 2 y was more clearly modified by 8-OHdG concentration (P-interaction = 0.04), where the omega-3 index was inversely associated with CES-D at 2 y, adjusted for baseline (ß = -1.66, SE = 0.66;P= 0.02), only among those with elevated 8-OHdG concentrations. Among individuals not taking antidepressant medications and in the top tertile of urinary 8-OHdG concentration, the omega-3 index was associated with significantly lower odds of a CES-D score ≥16 at baseline (OR: 0.72; 95% CI: 0.53, 0.96) but not at 2 y (OR: 0.83; 95% CI: 0.60, 1.15). CONCLUSIONS: An inverse association between the omega-3 index and depressive symptoms was observed among participants with elevated oxidative stress biomarkers. These data suggest that oxidative stress status may identify those who might benefit from ω-3 FA consumption to improve depressive symptoms.
Assuntos
Biomarcadores/sangue , Depressão/sangue , Depressão/tratamento farmacológico , Ácidos Graxos Ômega-3/sangue , Estresse Oxidativo , 8-Hidroxi-2'-Desoxiguanosina , Glicemia/metabolismo , Índice de Massa Corporal , Boston , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Estudos Transversais , Dano ao DNA , Desoxiguanosina/análogos & derivados , Desoxiguanosina/urina , Depressão/etnologia , Eritrócitos/metabolismo , Exercício Físico , Ácidos Graxos Ômega-3/administração & dosagem , Feminino , Seguimentos , Humanos , Insulina/sangue , Modelos Lineares , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Porto Rico/etnologia , Fatores Socioeconômicos , Inquéritos e Questionários , Triglicerídeos/sangueRESUMO
BACKGROUND: Folate status has been positively associated with cognitive function in many studies; however, some studies have observed associations of poor cognitive outcomes with high folate. In search of an explanation, we hypothesized that the association of folate with cognition would be modified by the interaction of high-folate status with a common 19-bp deletion polymorphism in the dihydrofolate reductase (DHFR) gene. To our knowledge, the cognitive effects of this gene have not been studied previously. OBJECTIVE: We examined the association between cognitive outcomes with the 19-bp deletion DHFR polymorphism, folate status, and their interaction with high or normal plasma folate. DESIGN: This was a pooled cross-sectional study of the following 2 Boston-based cohorts of community living adults: the Boston Puerto Rican Health Study and the Nutrition, Aging, and Memory in Elders study. Individuals were genotyped for the DHFR 19-bp deletion genotype, and plasma folate status was determined. Cognitive outcomes included the Mini-Mental State Examination, Center for Epidemiologic Studies Depression Scale, and factor scores for the domains of memory, executive function, and attention from a set of cognitive tests. RESULTS: The prevalence of the homozygous deletion (del/del) genotype was 23%. In a multivariable analysis, high folate status (>17.8 ng/mL) was associated with better memory scores than was normal-folate status (fourth-fifth quintiles compared with first-third quintiles: ß ± SE = -0.22 ± 0.06, P < 0.01). Carriers of the DHFR del/del genotype had worse memory scores (ß ± SE = -0.24 ± 0.10, P < 0.05) and worse executive scores (ß = -0.19, P < 0.05) than did those with the del/ins and ins/ins genotypes. Finally, we observed an interaction such that carriers of the del/del genotype with high folate had significantly worse memory scores than those of both noncarriers with high-folate and del/del carriers with normal-folate (ß-interaction = 0.26 ± 0.13, P < 0.05). CONCLUSIONS: This study identifies a putative gene-nutrient interaction that, if confirmed, would predict that a sizable minority carrying the del/del genotype might not benefit from high-folate status and could see a worsening of memory. An understanding of how genetic variation affects responses to high-folate exposure will help weigh risks and benefits of folate supplementation for individuals and public health.
Assuntos
Deficiência de Ácido Fólico/genética , Deleção de Genes , Transtornos da Memória/etiologia , Estado Nutricional , Polimorfismo Genético , Tetra-Hidrofolato Desidrogenase/genética , Negro ou Afro-Americano , Idoso , Idoso de 80 Anos ou mais , Boston/epidemiologia , Estudos de Coortes , Estudos Transversais , Feminino , Ácido Fólico/intoxicação , Deficiência de Ácido Fólico/enzimologia , Deficiência de Ácido Fólico/fisiopatologia , Estudos de Associação Genética , Hispânico ou Latino , Humanos , Masculino , Transtornos da Memória/epidemiologia , Pessoa de Meia-Idade , Nutrigenômica/métodos , Prevalência , Porto Rico/etnologia , Tetra-Hidrofolato Desidrogenase/metabolismo , População BrancaRESUMO
BACKGROUND: Associations of either insulin receptor substrate 1 (IRS1) variants or circulating 25-hydroxyvitamin D [25(OH)D] with type 2 diabetes (T2D) and insulin resistance (IR) are inconsistent. This study sought to determine whether circulating 25(OH)D modulates the association of a potentially functional variant at IRS1 (rs2943641) with insulin resistance. METHOD: Interaction between IRS1 rs2943641 and circulating 25(OH)D on homeostasis model assessment for IR (HOMA-IR) was examined in the Boston Puerto Rican Health Study (BPRHS) (n = 1144). Replication was performed in the African-American (n = 1126), non-Hispanic white (n = 1967), and Hispanic (n = 1241) populations of the Multi-Ethnic Study of Atherosclerosis (MESA) with genotypes of 3 IRS1 variants, rs2972144, rs1515104, and rs2673142, which are tag single nucleotide polymorphisms (SNPs) and in strong linkage disequilibrium with rs2943641. RESULTS: Higher circulating 25(OH)D was associated with lower risk of T2D and IR in BPRHS women homozygous for minor allele rs2943641T. Consistently, in each of 3 MESA populations, HOMA-IR and insulin decreased more evidently with higher circulating 25(OH)D in women of the rs2943641TT genotype than in carriers of the major allele (rs2943641C). Metaanalysis indicated significant and consistent interactions between circulating 25(OH)D and IRS1 variants on HOMA-IR (log transformed) [pooled ß = -0.008, 95% CI: -0.016 to -0.001, P interaction = 0.004] and insulin (log transformed) (pooled ß = -0.006, 95% CI: -0.011 to -0.002, P interaction = 0.023) in 3065 women of the 4 populations. CONCLUSIONS: Participants with different genotypes of IRS1 rs2943641 exhibit differential benefit from high circulating 25(OH)D for the reduction of insulin resistance and T2D risk. This gene-nutrient interaction, which appears to be limited to women, warrants further examination in randomized controlled trials of vitamin D supplementation.
Assuntos
Etnicidade , Proteínas Substratos do Receptor de Insulina/sangue , Resistência à Insulina/etnologia , Resistência à Insulina/genética , Polimorfismo de Nucleotídeo Único , Vitamina D/análogos & derivados , Feminino , Nível de Saúde , Humanos , Proteínas Substratos do Receptor de Insulina/genética , Masculino , Porto Rico/etnologia , Fatores de Risco , Vitamina D/sangueRESUMO
BACKGROUND: Although dietary treatments can successfully reduce blood lipids in hypercholesterolemic subjects, individual variation in that response has on occasion been linked to allelic differences. SNP rs12449157 has shown association with HDL-C concentrations in GWAS and falls in the glucose-fructose oxidoreductase domain containing 2 (GFOD2) locus. Of interest, previous data suggest that this SNP may be under environmentally driven selection. Thus, the aim of this study was to assess if rs12449157 may mediate the response of lipid traits to a dietary supplementation (DS) with soy protein and soluble fiber in a Mexican population with hypercholesterolemia. METHODS: Forty-one subjects with hypercholesterolemia were given a low saturated fat diet (LSFD) for 1 month, followed by a LSFD+DS that included 25 g of soy protein and 15 g of soluble fiber (S/SF) daily for 2 months. Anthropometric, clinical, biochemical and dietary variables were determined. We analyzed the gene-diet interaction between the GFOD2 genotype, with the minor allele frequency of 0.24, and the DS on total cholesterol (TC) and LDL-C concentrations. RESULTS: Hypercholesterolemic subjects with GFOD2 rs12449157 G allele had higher serum TC and LDL-C at the baseline and showed a greater response to the LSCD+S/SF (-83.9 and -57.5mg/dl, respectively) than those with GFOD2 AA genotype (-40.1 and -21.8 mg/dl, respectively) (P=0.006 for TC, 0.025 for LDL-C, respectively). CONCLUSION: The observed differences in allele-driven, diet-induced changes in blood lipids may be the result of a recent environmentally driven selection on the rs12449157 minor allele. Variation in the GFOD2 gene contributes to the genetic basis for a differential response to a cholesterol- or lipid-lowering diet.
Assuntos
LDL-Colesterol/sangue , Fibras na Dieta/administração & dosagem , Hipercolesterolemia/genética , Oxirredutases/genética , Polimorfismo de Nucleotídeo Único , Proteínas de Soja/administração & dosagem , Adulto , Suplementos Nutricionais , Feminino , Frequência do Gene , Estudos de Associação Genética , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/dietoterapia , Masculino , México , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
OBJECTIVE: Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional endocytic receptor that is highly expressed in adipocytes and the hypothalamus. Animal models and in vitro studies support a role for LRP1 in adipocyte metabolism and leptin signaling, but genetic polymorphisms have not been evaluated for obesity in people. DESIGN AND METHODS: We examined whether dietary fats (eg., saturated, polyunsaturated) modulated the association of LRP1 rs1799986 with anthropometric traits. We studied a population-based sample of Puerto Ricans (n = 920, aged 45-74 y) living in the Boston area.We examined whether dietary fats (eg., saturated, polyunsaturated) modulated the association of LRP1 rs1799986 with anthropometric traits. We studied a population-based sample of Puerto Ricans (n = 920, aged 45-74 y) living in the Boston area. RESULTS: In multivariable linear regression models, we dichotomized saturated fat intake and found significant interaction terms between total saturated fatty acids and LRP1 rs1799986 genotype for BMI (P=0.006) and hip (P = 0.002). High intake of saturated fat was associated with higher BMI (P = 0.001), waist (P = 0.008) and hip (P=0.003) in minor allele carriers (CT+TT) compared to CC participants. Further analysis of dichotomized individual saturated fatty acids revealed that interactions were strongest for two individual longer chain fatty acids. High intake of palmitic acid (C16:0; P = 0.0007) and high stearic acid intake (C18:0; P = 0.005) were associated with higher BMI in T carriers. Interactions were not detected for polyunsaturated fatty acids. CONCLUSIONS: Gene-diet interactions at the LRP1 locus support the hypothesis that susceptibility to weight gain based on saturated fatty acids is modified by genotype and possibly by chain length. These results may facilitate the development of a panel of genetic candidates for use in optimizing dietary recommendations for obesity management.