Acylcarnitines are associated with lower depressive symptomatology in a mainland puerto rican cohort.

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.

Association of BCAT2 and BCKDH polymorphisms with clinical, anthropometric and biochemical parameters in young adults.

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.

FADS1 and ELOVL2 polymorphisms reveal associations for differences in lipid metabolism in a cross-sectional population-based survey of Brazilian men and women.

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.

Development of a Genetic Score to Predict an Increase in HDL Cholesterol Concentration After a Dietary Intervention in Adults with Metabolic Syndrome.

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 ∼440 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.

Genetic admixture and body composition in Puerto Rican adults from the Boston Puerto Rican Osteoporosis Study.

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.

The Omega-3 Index Is Inversely Associated with Depressive Symptoms among Individuals with Elevated Oxidative Stress Biomarkers.

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.

Dihydrofolate reductase 19-bp deletion polymorphism modifies the association of folate status with memory in a cross-sectional multi-ethnic study of adults.

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.

Circulating 25-hydroxyvitamin D, IRS1 variant rs2943641, and insulin resistance: replication of a gene-nutrient interaction in 4 populations of different ancestries.

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.

Effect of a GFOD2 variant on responses in total and LDL cholesterol in Mexican subjects with hypercholesterolemia after soy protein and soluble fiber supplementation.

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.

Low-density lipoprotein receptor-related protein 1 variant interacts with saturated fatty acids in Puerto Ricans.

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.

Carbohydrate nutrition differs by diabetes status and is associated with dyslipidemia in Boston Puerto Rican adults without diabetes.

Puerto Rican adults have a greater prevalence of type 2 diabetes (T2D) and lower HDL-cholesterol (HDL-C) than the general U.S. population. Carbohydrate nutrition may play a role in this disparity. Cross-sectional analyses included data from 1219 Puerto Ricans aged 45-75 y enrolled in the Boston Puerto Rican Health Study. Using the Pearson chi-square test and ANCOVA, lifestyle characteristics and dietary intake, as assessed by semiquantitative FFQ, were compared by T2D status based on fasting plasma glucose concentration and medication use. Food source rankings for carbohydrate, dietary glycemic load (GL), and fiber were obtained using the SAS procedure PROC RANK. Geometric mean plasma HDL-C and TG concentrations were compared across quintiles of dietary carbohydrate, glycemic index (GI), GL, and fiber by using ANCOVA and tests for linear trend. In multivariable analyses, individuals with T2D (39.5%) had lower dietary carbohydrate, GL, and total sugar intake from lower intake of sugar, fruit drinks, and soda compared with those without T2D. In individuals without T2D, dietary carbohydrate and GL were inversely associated with HDL-C (P < 0.0001). Associations between dietary fiber and HDL-C were confounded by carbohydrate intake, apparently from concurrent consumption of legumes with white rice, a refined carbohydrate food. No associations were observed between carbohydrate, dietary GI, GL, or fiber and TG. In conclusion, individuals with T2D showed evidence of dietary modification. Among those without diabetes, a high intake of refined carbohydrates was associated with decreased HDL-C. Longitudinal research on carbohydrate nutrition in relation to diabetes risk factors and blood lipids in Puerto Ricans is warranted.

Acculturation and sociocultural influences on dietary intake and health status among Puerto Rican adults in Massachusetts.

BACKGROUND: Previous studies have shown negative consequences of acculturation on lifestyle factors, health status, and dietary intake of Hispanic immigrants in the US. Despite prevalent type 2 diabetes and low socioeconomic status (SES) among Puerto Rican adults living on the US mainland, little is known about acculturation in this group. OBJECTIVE: We investigated associations among acculturation, lifestyle characteristics, health status, and carbohydrate nutrition in Puerto Rican adults. A secondary objective was to investigate possible confounding and/or effect modification on these associations by SES. DESIGN: Cross-sectional data from the Boston Puerto Rican Health Study, which included 1219 Puerto Ricans in the Boston area, aged 45-75 years. STATISTICAL ANALYSES: Characteristics were compared using ANCOVA, linear trend and Pearson's chi-square tests across quartiles of acculturation. Tests for interaction by poverty status were conducted. Proportional contributions of foods to intake of total carbohydrate and fiber were assessed using SAS RANK. RESULTS: Levels of acculturation were low, despite young age at first arrival to the US mainland (25.4 ± 12.3 y) and long length of stay (34.2 ± 12.2 y). Greater English language use was associated with higher SES, alcohol consumption, physical activity, better perceived health, and less central obesity. Acculturation was associated with lower legume fiber and greater cereal fiber intake. Among those above the poverty threshold, acculturation was associated with lower dietary glycemic index and starch intake, and greater fruit and non-starchy vegetable intake. CONCLUSIONS: In contrast to studies with Mexican Americans, the association of acculturation with dietary quality in these Puerto Rican adults was mixed, but tended toward better carbohydrate quality. Dietary recommendations should include maintenance of traditional, healthful dietary practices including consumption of legumes, but also reduction in refined grains, and greater inclusion of fruit, non-starchy vegetables, and whole grains. Interventions to improve access to better quality carbohydrate sources are necessary for this group disproportionately affected by diabetes.

Association between BDNF rs6265 and obesity in the Boston Puerto Rican Health Study.

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.

The folate hydrolase 1561C>T polymorphism is associated with depressive symptoms in Puerto Rican adults.

OBJECTIVE: To examine the associations between variants of genes involved in the uptake, retention, and metabolism of folate and depressive symptoms and to analyze whether such associations are direct or through mediation by folate or homocysteine. METHODS: We performed a cross-sectional analysis of data from 976 Puerto Rican adults, aged 45 to 75 years, residing in the greater Boston area, Massachusetts. Twelve single nucleotide polymorphisms (SNPs) in genes involved in folate uptake, retention, and metabolism were investigated. These include FOLH1 (folate hydrolase), FPGS (folate polyglutamate synthase), GGH (γ-glutamyl hydrolase), MTHFR (methylenetetrahydrofolate reductase), MTR (methionine synthase), PCFT (proton-coupled folate transporter), and RFC1 (reduced folate carrier 1). The Center for Epidemiologic Studies Depression Scale (CES-D) was used to measure depressive symptoms. RESULTS: The FOLH1 rs61886492 C>T (or 1561C>T) polymorphism was significantly associated with lower CES-D score (p = .0025) after adjusting for age, sex, population admixture, smoking, and educational attainment. Individuals with the TT and TC genotypes were 49% less likely (odds ratio = 0.51, 95% confidence interval = 0.29-0.89) to report mild depressive symptoms (CES-D score ≥16 and ≤26) and 64% less likely (odds ratio = 0.36, 95% confidence interval = 0.18-0.69) to report moderate to severe depressive symptoms (CES-D score >26), compared with those with the CC genotype. No significant mediation effects by plasma folate or homocysteine on the associations between this single nucleotide polymorphism and CES-D score were observed. CONCLUSIONS: The FOLH1 1561C>T polymorphism may be associated with the risk of depressive symptoms.

Development of a cardiovascular risk score for use in low- and middle-income countries.

Summary measures of cardiovascular risk have long been used in public health, but few include nutritional predictors despite extensive evidence linking diet and heart disease. Study objectives were to develop and validate a novel risk score in a case-control study of myocardial infarction (MI) conducted in Costa Rica during 1994-2004. After restricting the data set to healthy participants (n = 1678), conditional logistic regression analyses modeled associations of lifestyle factors (unhealthy diet, decreased physical activity, smoking, waist:hip ratio, low or high alcohol intake, and low socioeconomic status) with risk for MI. Using the estimated coefficients as weights for each component, a regression model was fit to assess score performance. The score was subsequently validated in participants with a history of chronic disease. Higher risk score values were associated with a significantly increased risk of MI [OR = 2.72 (95% CI = 2.28-3.24)]. The findings were replicated in a model (n = 1392) that included the best covariate measures available in the study [OR = 2.71 (95% CI = 2.26-3.26)]. Performance of the score in different subsets of the study population showed c-statistics ranging from 0.63 to 0.67. The new score presents a quantitative summary of modifiable cardiovascular risk factors in the study population.

Interactions between genetic variants of folate metabolism genes and lifestyle affect plasma homocysteine concentrations in the Boston Puerto Rican population.

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 677C→T, FOLH1 1561C→T, FOLH1 rs647370 and PCFT 928A→G interacted significantly with smoking for Hcy. MTHFR 1298A→C (P = 0·040) and PCFT 928A→G (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 2756A→G 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.

Adherence to an (n-3) fatty acid/fish intake pattern is inversely associated with metabolic syndrome among Puerto Rican adults in the Greater Boston area.

Combinations of fatty acids may affect risk of metabolic syndrome. Puerto Ricans have a disproportionate number of chronic conditions compared with other Hispanic groups. We aimed to characterize fatty acid intake patterns of Puerto Rican adults aged 45-75 y and living in the Greater Boston area (n = 1207) and to examine associations between these patterns and metabolic syndrome. Dietary fatty acids, as a percentage of total fat, were entered into principle components analysis. Spearman correlation coefficients were used to examine associations between fatty acid intake patterns, nutrients, and food groups. Associations with metabolic syndrome were analyzed by using logistic regression and general linear models with quintiles of principal component scores. Four principal components (factors) emerged: factor 1, short- and medium-chain SFA/dairy; factor 2, (n-3) fatty acid/fish; factor 3, very long-chain (VLC) SFA and PUFA/oils; and factor 4, monounsaturated fatty acid/trans fat. The SFA/dairy factor was inversely associated with fasting serum glucose concentrations (P = 0.02) and the VLC SFA/oils factor was negatively related to waist circumference (P = 0.008). However, these associations were no longer significant after additional adjustment for BMI. The (n-3) fatty acid/fish factor was associated with a lower likelihood of metabolic syndrome (Q5 vs. Q1: odds ratio: 0.54, 95% CI: 0.34, 0.86). In summary, principal components analysis of fatty acid intakes revealed 4 dietary fatty acid patterns in this population. Identifying optimal combinations of fatty acids may be beneficial for understanding relationships with health outcomes given their diverse effects on metabolism.

Urinary 8-hydroxy-2-deoxyguanosine and cognitive function in Puerto Rican adults.

DNA oxidative stress has been suggested as an important pathogenic mechanism in cognitive impairment and dementia. With baseline data collected from 2004 to 2008, the authors examined whether urinary 8-hydroxy-2-deoxyguanosine (8-OHdG), a biomarker of global DNA oxidation, was associated with cognitive function in a sample of 1,003 Puerto Rican adults, aged 45-75 years, living in Boston, Massachusetts, and the surrounding area. Cognitive function was measured by using a battery of 7 tests: the Mini-Mental State Examination, word list learning, digit span, clock drawing and figure copying, Stroop, and verbal fluency tests. The primary outcome was a global cognitive score, averaging standardized scores across all cognitive tests. A higher 8-OHdG concentration was significantly associated with lower global cognitive scores, after adjustment for age, education, status of the gene for apolipoprotein E (APOE), and other covariates (P(trend) = 0.01). The difference in the global score, comparing participants in the 2 extreme 8-OHdG quartiles, was -0.11 (95% confidence interval: -0.20, -0.02), which was equivalent to accelerating cognitive aging by about 4 years, as observed in this population. Prospective studies are needed to elucidate whether elevated urinary 8-OHdG concentrations can predict the rate of cognitive decline and incident dementia.

Allostatic load is associated with chronic conditions in the Boston Puerto Rican Health Study.

Puerto Ricans living in the United States mainland present multiple disparities in prevalence of chronic diseases, relative to other racial and ethnic groups. Allostatic load (AL), or the cumulative wear and tear of physiological responses to stressors such as major life events, social and environmental burden, has been proposed as a possible mechanism for the inequalities observed in minority groups, but has not been studied in Puerto Ricans. The aim of this study was to determine the association of AL to six chronic diseases (abdominal obesity, hypertension, diabetes, and self-reported cardiovascular disease (CVD), arthritis and cancer) in Puerto Ricans, and to contrast AL to metabolic syndrome (MetS). Participants of the Boston Puerto Rican Health Study (n=1116, ages 45-75 years) underwent a home-based interview, where questionnaires were completed and biological samples collected. A summary definition of AL was constructed using clinically-defined cutoffs and medication use for 10 physiological parameters in different body systems. Logistic regression models were run to determine associations between AL score and disease status, controlling for age, sex, smoking, alcohol use, physical activity, total fat intake and energy intake. Parallel models were also run with MetS score replacing AL. We found that increasing categories of AL score were significantly associated with abdominal obesity, hypertension, diabetes and self-reported cardiovascular disease (CVD) and arthritis, but not with self-reported cancer. The strength of associations of AL with all conditions, except diabetes and cancer, was similar to or larger than those of MetS score. In conclusion, Puerto Rican older adults experienced physiological dysregulation that was associated with increased odds of chronic conditions. AL was more strongly associated with most conditions, compared to MetS, suggesting that this cumulative measure may be a better predictor of disease. These results have prospective research implications for Puerto Ricans and other ethnic groups.

The Boston Puerto Rican Health Study, a longitudinal cohort study on health disparities in Puerto Rican adults: challenges and opportunities.

BACKGROUND: The Boston Puerto Rican Health Study is an ongoing longitudinal cohort study designed to examine the role of psychosocial stress on presence and development of allostatic load and health outcomes in Puerto Ricans, and potential modification by nutritional status, genetic variation, and social support. METHODS: Self-identified Puerto Ricans, aged 45-75 years and residing in the Boston, MA metro area, were recruited through door-to-door enumeration and community approaches. Participants completed a comprehensive set of questionnaires and tests. Blood, urine and salivary samples were extracted for biomarker and genetic analysis. Measurements are repeated at a two-year follow-up. RESULTS: A total of 1500 eligible participants completed baseline measurements, with nearly 80% two-year follow-up retention. The majority of the cohort is female (70%), and many have less than 8th grade education (48%), and fall below the poverty level (59%). Baseline prevalence of health conditions is high for this age range: considerable physical (26%) and cognitive (7%) impairment, obesity (57%), type 2 diabetes (40%), hypertension (69%), arthritis (50%) and depressive symptomatology (60%). CONCLUSIONS: The enrollment of minority groups presents unique challenges. This report highlights approaches to working with difficult to reach populations, and describes some of the health issues and needs of Puerto Rican older adults. These results may inform future studies and interventions aiming to improve the health of this and similar communities.