RESUMO
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
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.
Assuntos
Ácidos Graxos/metabolismo , Variação Genética , Hispânico ou Latino/genética , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Obesidade/etnologia , Adiposidade/efeitos dos fármacos , Adiposidade/genética , Idoso , Índice de Massa Corporal , Boston/epidemiologia , Dieta , Gorduras na Dieta/administração & dosagem , Ingestão de Energia , Ácidos Graxos/administração & dosagem , Feminino , Frequência do Gene , Interação Gene-Ambiente , Loci Gênicos , Predisposição Genética para Doença , Genótipo , Hispânico ou Latino/estatística & dados numéricos , Humanos , Leptina/sangue , Estilo de Vida , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Avaliação Nutricional , Obesidade/genética , Fenótipo , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Porto Rico/etnologia , Inquéritos e QuestionáriosRESUMO
Brain-derived neurotrophic factor (BDNF) has been associated with regulation of body weight and appetite. The goal of this study was to examine the interactions of a functional variant (rs6265) in the BDNF gene with dietary intake for obesity traits in the Boston Puerto Rican Health Study. BDNF rs6265 was genotyped in 1147 Puerto Rican adults and examined for association with obesity-related traits. Men (n = 242) with the GG genotype had higher BMI (P = 0.009), waist circumference (P = 0.002), hip (P = 0.002), and weight (P = 0.03) than GA or AA carriers (n = 94). They had twice the risk of being overweight (BMI ≥ 25) relative to GA or AA carriers (OR = 2.08, CI = 1.02-4.23, and P = 0.043). Interactions between rs6265 and polyunsaturated fatty acids (PUFA) intake were associated with BMI, hip, and weight, and n-3 : n-6 PUFA ratio with waist circumference in men. In contrast, women (n = 595) with the GG genotype had significantly lower BMI (P = 0.009), hip (P = 0.029), and weight (P = 0.027) than GA or AA carriers (n = 216). Women with the GG genotype were 50% less likely to be overweight compared to GA or AA carriers (OR = 0.05, CI = 0.27-0.91, and P = 0.024). In summary, BDNF rs6265 is differentially associated with obesity risk by sex and interacts with PUFA intake influencing obesity traits in Boston Puerto Rican men.
Assuntos
Índice de Massa Corporal , Fator Neurotrófico Derivado do Encéfalo/genética , Ácidos Graxos Insaturados/administração & dosagem , Obesidade/genética , Idoso , Boston , Dieta , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Porto Rico/etnologiaRESUMO
OBJECTIVE: To investigate genetic and lifestyle factors and their interactions on plasma homocysteine (Hcy) concentrations in the Boston Puerto Rican population. DESIGN: Cross-sectional study. Plasma concentrations of Hcy, folate, vitamin B12 and pyridoxal phosphate were measured, and genetic polymorphisms were determined. Data on lifestyle factors were collected in interviews. SETTING: A population survey of health and nutritional measures. SUBJECTS: A total of 994 Puerto Rican men and women residing in the Boston metropolitan area. RESULTS: Smoking status was positively associated with plasma Hcy. Genetic polymorphisms MTHFR 677CâT, FOLH1 1561CâT, FOLH1 rs647370 and PCFT 928AâG interacted significantly with smoking for Hcy. MTHFR 1298AâC (P = 0·040) and PCFT 928AâG (P = 0·002) displayed significant interactions with alcohol intake in determining plasma Hcy. Subjects with PCFT 928GG genotype had significantly higher plasma Hcy concentrations compared with carriers of the A allele (AA+AG; P = 0·030) among non-drinking subjects. When consuming alcohol, GG subjects had lower plasma Hcy levels compared with AA+AG subjects. Physical activity interacted significantly with MTR 2756AâG in determining plasma Hcy (P for interaction = 0·002). Smoking interacted with physical activity for plasma Hcy (P for interaction = 0·023). CONCLUSIONS: Smoking and drinking were associated plasma Hcy concentrations. Genetic variants involved in folate metabolism further modify the effects of lifestyle on plasma Hcy.
Assuntos
Ácido Fólico/sangue , Interação Gene-Ambiente , Homocisteína/sangue , Estilo de Vida/etnologia , Polimorfismo de Nucleotídeo Único , Idoso , Consumo de Bebidas Alcoólicas/etnologia , Alelos , Boston , Estudos Transversais , Feminino , Predisposição Genética para Doença , Genótipo , Glutamato Carboxipeptidase II/genética , Glutamato Carboxipeptidase II/metabolismo , Humanos , Modelos Lineares , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/metabolismo , Pessoa de Meia-Idade , Atividade Motora , Transportador de Folato Acoplado a Próton/genética , Transportador de Folato Acoplado a Próton/metabolismo , Porto Rico/etnologia , Fatores Sexuais , Fumar/etnologia , Vitamina B 12/sangueRESUMO
BACKGROUND: The S-adenosylmethionine synthetase type 1 (MAT1A) gene encodes a key enzyme in one-carbon nutrient metabolism. OBJECTIVE: This study aimed to determine the association of MAT1A variants with homocysteine, DNA damage, and cardiovascular disease (CVD). DESIGN: Eight variants of MAT1A were examined for associations with hypertension, stroke, CVD, homocysteine, and DNA damage in 1006 participants of the Boston Puerto Rican Health Study. Two variants were replicated in 1147 participants of the Nutrition, Aging, and Memory in Elders Study. RESULTS: Two variants and haplotypes were strongly associated with hypertension and stroke, independent of methylenetetrahydrofolate reductase (MTHFR) variants. Homozygotes of the MAT1A d18777A (rs3851059) allele had a significantly greater likelihood of stroke (odds ratio: 4.30; 95% CI: 1.34, 12.19; P = 0.006), whereas 3U1510A (rs7087728) homozygotes had a lower likelihood of hypertension (odds ratio: 0.67; 95% CI: 0.48, 0.95; P = 0.022) and stroke (odds ratio: 0.35; 95% CI: 0.15, 0.82; P = 0.015). A similar trend of association was observed in a second elderly population. Furthermore, strong interactions between MAT1A genotypes and vitamin B-6 status were found. Carriers of the nonrisk allele 3U1510A had a lower 8-hydroxydeoxyguanosine concentration--a biomarker of oxidative DNA damage--when plasma vitamin B-6 was high, whereas homozygotes for the risk-allele 3U1510G had higher 8-hydroxydeoxyguanosine concentrations, regardless of vitamin B-6 status. CONCLUSIONS: MAT1A variants were strongly associated with hypertension and stroke. Improving folate and vitamin B-6 status might decrease the CVD risk of only a subset of the population, depending on genotype. These findings suggest that impairments in methylation activity, independent of homocysteine, have an effect on CVD risk.
Assuntos
Dano ao DNA , Ácido Fólico/sangue , Variação Genética , Hipertensão/genética , Metionina Adenosiltransferase/genética , Acidente Vascular Cerebral/genética , Vitamina B 6/sangue , Adulto , Idoso , Boston , Doenças Cardiovasculares/genética , Transtornos Cognitivos/genética , Feminino , Genótipo , Homocisteína/sangue , Humanos , Hipertensão/prevenção & controle , Estilo de Vida , Masculino , Memória , Pessoa de Meia-Idade , Porto Rico/etnologia , Acidente Vascular Cerebral/prevenção & controleRESUMO
OBJECTIVE: Puerto Ricans experience a high prevalence of several chronic conditions, including metabolic syndrome. Genetic variants of the CD36 gene have been associated with metabolic syndrome. We aimed to determine the association between 6 single nucleotide polymorphisms (SNPs) for CD36 and metabolic syndrome and its components in Puerto Ricans (45-75 year) living in the Greater Boston area. METHODS: Associations between each SNP, metabolic syndrome and its components were examined using multivariate logistic regression models. Haplotype trend regression analysis was used to determine associations between haplotypes and metabolic syndrome. RESULTS: For two SNPs of CD36 (rs1049673 and rs3211931), homozygous subjects of the minor allele (G and T, respectively) were associated with a higher likelihood of metabolic syndrome (odds ratio (OR) (95% confidence interval (CI)): 1.89 (1.0, 3.5) and 1.77 (1.0, 3.1), respectively) relative to carriers of the major allele. Although CD36 haplotypes were not significantly associated with metabolic syndrome overall (global significance, P=0.23), one haplotype (G-C-C vs. C-C-C (reference haplotype)) was marginally associated (P=0.049). CONCLUSION: SNPs of CD36 were associated with metabolic syndrome in Puerto Ricans. Prospective studies should further explore the role of CD36 variants in the development of this condition.
Assuntos
Antígenos CD36/genética , Síndrome Metabólica/genética , Adulto , Boston/epidemiologia , Hispânico ou Latino/genética , Humanos , Síndrome Metabólica/epidemiologia , Polimorfismo de Nucleotídeo Único , Porto Rico/etnologiaRESUMO
Apolipoprotein A5 (APOA5) and lipoprotein lipase (LPL) proteins interact functionally to regulate lipid metabolism, and single-nucleotide polymorphisms (SNPs) for each gene have also been associated independently with obesity risk. Evaluating gene combinations may be more effective than single SNP analyses in identifying genetic risk, but insufficient minor allele frequency (MAF) often limits evaluations of potential epistatic relationships. Populations with multiple ancestral admixtures may provide unique opportunities for evaluating genetic interactions. We examined relationships between LPL m107 (rs1800590) and APOA5 S19W (rs3135506) and lipid and anthropometric measures in Caribbean origin Hispanics (n = 1,019, aged 45-75 years) living in the Boston metropolitan area. Significant interaction terms between LPL m107 and APOA5 S19W were observed for BMI (P = 0.003) and waist circumference (P = 0.019). Higher BMI (P = 0.001), waist (P = 0.011) and hip (P = 0.026) circumference were observed in minor allele (G) carriers for LPL m107 who also carried the APOA5 S19W minor allele (G). Additionally, extreme obesity (BMI > or = 40 kg/m(2)) risk was higher (odds ratio = 4.02; 95% confidence interval: 1.81-8.91; global P = 0.008) for minor allele carriers for both SNPs (LPL TG+GG, APOA5 CG+GG) compared to major allele carriers for both SNPs. In summary, we identified significant interactions for APOA5 S19W and LPL m107 for obesity in Caribbean Hispanics. Population-specific MAFs increase the difficulties of replicating gene-gene interactions, but may support the hypothesis that combinations of frequencies in selected genes could heighten obesity susceptibility in a given population. Analyses of gene-gene interactions may improve understanding of genetically based obesity risk, and underscore the need for further study of groups with multiple ancestral admixtures.