Traditional rural dietary pattern and all-cause mortality in a prospective cohort study of elderly Costa Ricans: the Costa Rican Longevity and Healthy Aging Study (CRELES).

BACKGROUND: Costa Rica is experiencing a fast demographic aging. Healthy diets may help to ameliorate the burden of aging-related conditions. OBJECTIVE: This study aimed to investigate the association of a traditional dietary pattern and 2 of its major components (beans and rice) with all-cause mortality among elderly Costa Ricans. METHODS: The Costa Rican Longevity and Healthy Aging Study (CRELES), a prospective cohort study of 2827 elderly Costa Ricans (60+ y at baseline), started in 2004. We used a food frequency questionnaire (FFQ) to assess usual diet. We calculated dietary patterns using principal component analysis. Multivariate energy-adjusted proportional-hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Over a 15-y follow-up, encompassing 24,304 person-years, 1667 deaths occurred. The traditional Costa Rican dietary pattern was more frequent in rural parts of the country, and it was inversely associated with all-cause mortality. Subjects in the fifth quintile of intake had 18% lower all-cause mortality than those in the first quintile (HR: 0.82; 95% CI: 0.69, 0.98; P-trend = 0.01), particularly among males (HR: 0.73; 95% CI: 0.56, 0.95). Bean intake was associated with lower all-cause mortality among all subjects (HR: 0.79; 95% CI: 0.68, 0.91, highest compared with lowest tertile) and in sex-stratified analysis. Rice consumption was inversely associated with all-cause mortality solely among males (HR: 0.75; 95% CI: 0.60, 0.94, highest compared with lowest tertile). CONCLUSIONS: Our results suggest that a traditional Costa Rican rural dietary pattern is associated with lower all-cause mortality in elderly Costa Ricans. Beans, a major component of this traditional dietary pattern, was also associated with lower all-cause mortality. These findings could have important implications for public health, given the nutritional transition and the reduction of intake of traditional diets in Latin American countries.

Micro- and Macronutrient Intake in Elderly Costa Ricans: The Costa Rican Longevity and Healthy Aging Study (CRELES).

Costa Rica, a middle-income country in Central America, has a life expectancy similar or even higher than richer countries. This survival advantage is more evident among the elderly, who have one of the lowest mortality rates in the world. Dietary factors may play a role in this extended longevity. We have shown that a traditional rural diet is associated with longer leukocyte telomere length-a biomarker of aging-among elderly Costa Ricans. In the present study, we used data from the Costa Rican Longevity and Healthy Aging Study (CRELES) to characterize further rural and urban diets of the elderly (60+ years). A validated food frequency questionnaire was used to assess usual diet. We used energy-adjusted regression models to compare the intake of micro- and macronutrients between rural and urban regions of the country. Elderly rural residents had a higher consumption of carbohydrates (but lower glycemic index), fiber, dietary iron, and used more palm oil for cooking than elderly urban dwellers. On the other hand, elderly subjects living in urban areas had a higher intake of total fat, mono and polyunsaturated fat, alcohol and dietary calcium compared to elderly rural residents. Our results are similar to earlier reports of middle-aged Costa Ricans and add to the characterization of diet differences in rural and urban regions of the country.

DNA Methylation Is a Potential Biomarker for Cardiometabolic Health in Mexican Children and Adolescents.

DNA methylation (DNAm) is a plausible mechanism underlying cardiometabolic abnormalities, but evidence is limited among youth. This analysis included 410 offspring of the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) birth cohort followed up to two time points in late childhood/adolescence. At Time 1, DNAm was quantified in blood leukocytes at long interspersed nuclear elements (LINE-1), H19, and 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD-2), and at Time 2 in peroxisome proliferator-activated receptor alpha (PPAR-α). At each time point, cardiometabolic risk factors were assessed including lipid profiles, glucose, blood pressure, and anthropometry. Linear mixed effects models were used for LINE-1, H19, and 11ß-HSD-2 to account for the repeated-measure outcomes. Linear regression models were conducted for the cross-sectional association between PPAR-α with the outcomes. DNAm at LINE-1 was associated with log glucose at site 1 [ß = -0.029, p = 0.0006] and with log high-density lipoprotein cholesterol at site 3 [ß = 0.063, p = 0.0072]. 11ß-HSD-2 DNAm at site 4 was associated with log glucose (ß = -0.018, p = 0.0018). DNAm at LINE-1 and 11ß-HSD-2 was associated with few cardiometabolic risk factors among youth in a locus-specific manner. These findings underscore the potential for epigenetic biomarkers to increase our understanding of cardiometabolic risk earlier in life.

Sedentary patterns and cardiometabolic risk factors in Mexican children and adolescents: analysis of longitudinal data.

BACKGROUND: Sedentary behavior is a modifiable risk factor for cardiometabolic health; however, the assessment of total sedentary time may not capture youth's highly active and interrupted activity patterns. This study examined the associations between sedentary activity patterns and cardiometabolic risk factors among Mexican youth, who have a disproportionate burden of metabolic diseases, using a repeated measure design out of a longitudinal data. METHODS: 570 subjects in the Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) birth cohort, who were followed up to three-time points during adolescence, were included. Bout duration, and frequency and percentages of waking time spent in specific intensities of activity, were quantified using ActiGraph wGT3X-BT wrist accelerometers. Self-reported questionnaires were used to query the usual duration of different sedentary behaviors. Outcomes were fasting lipid profile, markers for glucose homeostasis, anthropometry, and blood pressure. Associations were modeled using linear mixed-effects models, and isotemporal substitution approach was additionally used to assess the effect of replacing objectively assessed sedentary activity with other activity intensities, adjusting for potential confounders. RESULTS: Each hour of self-reported screen-based time was positively associated with diastolic blood pressure (mm Hg) [ß = 0.30, 95% confidence interval (95% CI) = 0.10, 0.51], and an hour of other sedentary time was associated with log serum glucose (mg/dL) [ß = 0.01, 95% CI = 0.004, 0.017]. Substitution models showed that replacing 5% of sedentary time with moderate to vigorous physical activity (MVPA) was associated with lower waist circumference (cm) [ß = - 1.35, 95% CI = - 1.91, - 0.79] and log serum triglycerides (mg/dL) [ß = - 0.11, 95% CI = - 0.18, - 0.03]. Substituting one uninterrupted sedentary bout with light activity was associated with lower insulin (µIU/mL) [ß = - 0.06, 95% CI = - 0.10, - 0.02]. CONCLUSIONS: Sedentary time was associated with cardiometabolic risk factors in Mexican youth in a context-specific manner. Replacing sedentary time with higher intensities was associated with improvements in some cardiometabolic markers.

Diet Quality Scores and Cardiometabolic Risk Factors in Mexican Children and Adolescents: A Longitudinal Analysis.

There is limited evidence for the effects of diet on cardiometabolic profiles during the pubertal transition. We collected repeated measures of diet quality and cardiometabolic risk factors among Mexican youth. This analysis included 574 offspring of the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) birth cohort followed up to three time points. Dietary Approaches to Stop Hypertension (DASH), alternate Mediterranean Diet (aMedDiet), and Children's Dietary Inflammatory Index (C-DIITM) scores were computed from food frequency questionnaires. Higher DASH and aMedDiet scores reflect a higher diet quality, and lower C-DII scores reflect an anti-inflammatory diet. Cardiometabolic risk factors were lipid profile, glucose homeostasis, blood pressure, and waist circumference. Linear mixed models were used between quartiles of each diet score and outcomes. Compared to the first quartile, the fourth DASH quartile was inversely associated with log serum insulin (µIU/mL) [ß = -0.19, p = 0.0034] and log-Homeostatic Model Assessment of Insulin Resistance [ß = -0.25, p = 0.0008]. Additionally, log serum triglycerides (mg/dL) was linearly associated with aMedDiet score [ß = -0.03, p = 0.0022]. Boys in the highest aMedDiet quartile had higher serum high-density lipoprotein cholesterol (mg/dL) [ß = 4.13, p = 0.0034] compared to the reference quartile. Higher diet quality was associated with a better cardiometabolic profile among Mexican youth.

Diet and Leukocyte Telomere Length in a Population with Extended Longevity: The Costa Rican Longevity and Healthy Aging Study (CRELES).

Elderly Costa Ricans have lower mortality rates compared to their counterparts from developed countries. Reasons for this survival advantage are not completely known. In the present study, we aimed to identify dietary factors associated with leukocyte telomere length (LTL), a marker of biologic aging, in the elderly population of Costa Rica. We conducted prospective analysis in 909 participants aged 60+ years from the Costa Rican Longevity and Healthy Aging Study (CRELES). We used a food frequency questionnaire to assess usual diet. We calculated dietary patterns using Principal Component Analysis (PCA). We used generalized linear models to examine the association of dietary patterns and food groups with leukocyte telomere length. We found two major dietary patterns explaining 9.15% and 7.18% of the total variation of food intake, respectively. The first dietary pattern, which represents a traditional Costa Rican rice and beans pattern, was more frequent in rural parts of the country and was positively associated with baseline LTL: ß (95% CI) = 42.0 base-pairs (bp) (9.9 bp, 74.1 bp) per one-unit increase of the traditional dietary pattern. In analysis of individual food groups, intake of grains was positively associated with baseline LTL: ß (95% CI) = 43.6 bp (13.9 bp, 73.3 bp) per one-serving/day increase of consumption of grains. Our results suggest that dietary factors, in particular a traditional food pattern, are associated with telomere length and may contribute to the extended longevity of elderly Costa Ricans.

Starchy Vegetables and Metabolic Syndrome in Costa Rica.

Only a few studies primarily examined the associations between starchy vegetables (other than potatoes) and metabolic syndrome (MetS). We aimed to evaluate the association between starchy vegetables consumption and MetS in a population-based sample of Costa Rican adults. We hypothesized that a higher overall intake of starchy vegetables would not be associated with higher MetS prevalence. In this cross-sectional study, log-binomial regression models were used to estimate prevalence ratios (PRs) of MetS across quintiles of total, unhealthy, healthy starchy vegetables, and individual starchy vegetables (potatoes, purple sweet potatoes, etc.), among 1881 Costa Rican adults. Least square means and 95% confidence intervals (CIs) from linear regression models were estimated for each MetS component by categories of starchy vegetable variables. Higher intakes of starchy vegetables were associated with a higher prevalence of MetS in crude models, but no significant trends were observed after adjusting for confounders. A significant inverse association was observed between total starchy and healthy starchy vegetables consumption and fasting blood glucose. In this population, starchy vegetables might be part of a healthy dietary pattern.

Admixture mapping and fine-mapping of type 2 diabetes susceptibility loci in African American women.

African American women are disproportionately affected by type 2 diabetes. Genetic factors may explain part of the excess risk. More than 100 genetic variants have been associated with risk of type 2 diabetes, but most studies have been conducted in white populations. Two genome-wide association studies (GWAS) in African Americans have identified three novel genetic variants only. We conducted admixture mapping using 2918 ancestral informative markers in 2632 cases of type 2 diabetes, and 2596 controls nested in the ongoing Black Women's Health Study cohort, with the goal of identifying genomic loci with local African ancestry associated with type 2 diabetes. In addition, we performed replication analysis of 71 previously identified index SNPs, and fine-mapped those genetic loci to identify better or new genetic variants associated with type 2 diabetes in African Americans. We found that individual African ancestry was associated with higher risk of type 2 diabetes. In addition, we identified two genomic regions, 3q26 and 12q23, with excess of African ancestry associated with higher risk of type 2 diabetes. Lastly, we replicated 8 out of 71 index SNPs from previous GWAS, including, for the first time in African Americans, the X-linked rs5945326 SNP near the DUSP9 gene. In addition, our fine-mapping efforts suggest independent signals at five loci. Our detailed analysis identified two genomic regions associated with risk of type 2 diabetes, and showed that many genetic risk variants are shared across ancestries.

Amerindian ancestry and extended longevity in Nicoya, Costa Rica.

OBJECTIVES: The aim of this study was to address the hypothesis that Amerindian ancestry is associated with extended longevity in the admixed population of Nicoya, Costa Rica. The Nicoya Peninsula of Costa Rica has been considered a "longevity island," particularly for males. METHODS: We estimated Amerindian ancestry using 464 ancestral informative markers in 20 old Nicoyans aged ≥99 years, and 20 younger Nicoyans (60-65 years). We used logistic regression to estimate odds ratio (OR) and 95% confidence interval (CI) of the association of Amerindian ancestry and longevity. RESULTS: Older Nicoyans had higher Amerindian ancestry compared to younger Nicoyans (43.3% vs 36.0%, P = .04). Each 10% increase of Amerindian ancestry was associated with more than twice the odds of being long-lived (OR = 2.32, 95% CI = 1.03-5.25). CONCLUSIONS AND IMPLICATIONS: To our knowledge, this is the first time that ancestry is implicated as a likely determinant of extended longevity. Amerindian-specific alleles may protect against early mortality. The identification of these protective alleles should be the focus of future studies.

Cross-sectional study of conjugated linoleic acid in adipose tissue and risk of diabetes.

BACKGROUND: Some experimental studies on conjugated linoleic acid (CLA) and insulin regulation suggested that CLA could be associated with risk of diabetes, but epidemiologic studies are lacking. OBJECTIVE: The aim of the study was to test whether the amount of CLA in adipose tissue is associated with risk of diabetes. DESIGN: A cross-sectional design was used to test the study hypothesis in 232 adults with diabetes and 1512 adults without diabetes who lived in Costa Rica. The cis-9, trans-11 and trans-10, cis-12 CLA isomers in adipose tissue and 48 other fatty acids were assessed by using gas chromatography. Prevalence ratios (PRs) and 95% CIs were estimated by using Poisson regression adjusted for potential confounders. RESULTS: The mean (±SD) percentage of total fatty acids of CLA for the cis-9, trans-11 isomer in adipose tissue was 0.57 ± 0.18% in adults without diabetes and 0.53 ± 0.17% in adults with diabetes (P = 0.0078). The trans-10, cis-12 CLA isomer was not detected in adipose tissue. The cis-9, trans-11 CLA isomer was associated with a lower risk of diabetes. In comparison with the first quintile, the PR (95% CI) for the fifth quintile was 0.48 (0.31, 0.76) (P-trend = 0.0005) in the basic and 0.46 (0.29, 0.72) (P-trend = 0.0002) in the multivariable model. Additional adjustment for other fatty acids in adipose tissue including trans-9 16:1, which is a fatty acid that was previously associated with diabetes, did not modify the results. CONCLUSION: The observed inverse association between the cis-9, trans-11 CLA in adipose tissue and diabetes risk is consistent with the hypothesis that CLA may be involved in insulin regulation.

Investigation of KIF6 Trp719Arg in a case-control study of myocardial infarction: a Costa Rican population.

BACKGROUND AND METHODOLOGY: The 719Arg allele of KIF6 (rs20455) was associated with coronary events in Caucasian participants of five prospective studies. We investigated whether this KIF6 variant was associated with non-fatal myocardial infarction (MI) in a case-control study of an admixed population from the Central Valley of Costa Rica. Genotypes of the KIF6 variant were determined for 4,134 men and women. Cases (1,987) had survived a first MI; controls (2,147) had no history of MI and were matched to cases by age, sex, and area of residence. We tested the association between the KIF6 719Arg allele and non-fatal MI by conditional logistic regression and adjusted for admixture of founder populations. PRINCIPAL FINDINGS: Compared with the reference Trp/Trp homozygotes, KIF6 719Arg carriers were not at significantly higher risk for non-fatal MI in this study after adjustment for traditional risk factors or admixture (OR= 1.12; 95%CI, 0.98-1.28). Heterozygotes of the KIF6 Trp719Arg variant were at increased risk of non-fatal MI: the adjusted odds ratio was 1.16 (95% confidence interval, 1.01-1.34), but this association would not be significant after a multiple testing correction. CONCLUSIONS/SIGNIFICANCE: We found that carriers of the KIF6 719Arg allele were not at increased risk of non-fatal MI in a case-control study of Costa Ricans living in the Central Valley of Costa Rica.

West African and Amerindian ancestry and risk of myocardial infarction and metabolic syndrome in the Central Valley population of Costa Rica.

Genetic ancestry and environmental factors may contribute to the ethnic differences in risk of coronary heart disease (CHD), metabolic syndrome (MS) or its individual components. The population of the Central Valley of Costa Rica offers a unique opportunity to assess the role of genetic ancestry in these chronic diseases because it derived from the admixture of a relatively small number of founders of Southern European, Amerindian, and West African origin. We aimed to determine whether genetic ancestry is associated with risk of myocardial infarction (MI), MS and its individual components in the Central Valley of Costa Rica. We genotyped 39 ancestral informative markers in cases (n = 1,998) with a first non-fatal acute MI and population-based controls (n = 1,998) matched for age, sex, and area of residence, to estimate individual ancestry proportions. Odds ratios (ORs) and 95% confidence intervals (95% CI) were estimated using conditional (MI) and unconditional (MS and its components) logistic regression adjusting for relevant confounders. Mean individual ancestry proportions in cases and controls were 57.5 versus 57.8% for the Southern European, 38.4 versus 38.3% for the Amerindian and 4.1 versus 3.8% for the West African ancestry. Compared with Southern European ancestry, each 10% increase in West African ancestry was associated with a 29% increase in MI, OR (95% CI) = 1.29 (1.07, 1.56), and with a 30% increase on the risk of hypertension, OR (95% CI) = 1.30 (1.00, 1.70). Each 10% increase in Amerindian ancestry was associated with a 14% increase on the risk of MS, OR (95% CI) = 1.14 (1.00, 1.30), and 20% increase on the risk of impaired fasting glucose, OR (95% CI) = 1.20 (1.01, 1.42). These results show that the high variability of admixture proportions in the Central Valley population offers a unique opportunity to uncover the genetic basis of ethnic differences on the risk of disease.

Gene expression and chromosomal location for susceptibility to Sjögren's syndrome.

Primary Sjögren's syndrome (SS) is a chronic inflammatory autoimmune disease affecting mainly the exocrine glands. Its physio-pathology is poorly understood and most of the knowledge has been related to the inflammatory component. The aim of this work was to evaluate gene expression profiling in fractions enriched in epithelial cells from labial salivary glands (LSGs) of patients with primary SS and identify chromosomal regions harboring susceptibility genes expressed in epithelial cells. A combined approach of gene expression and genome-wide association study was used. Enriched epithelial cell fractions were obtained from LSGs of patients and controls. Amplified total RNA was labeled and hybridized to 10K cDNA microarrays. Results were normalized and subjected to statistical and functional analysis. A genome-wide microsatellite screen at 10 cM resolution (393 markers) was performed. In salivary gland-epithelial cells from patients 528 genes were expressed differentially in comparison to controls. Pathways not previously linked to disease were found to be altered. Twenty-eight and 15 genes associated with apoptosis were up-regulated and down regulated, respectively. Interferon-related genes, most of which participated in interferon signaling, were also found to be up-regulated. From the genome-wide screen, 6 markers showed evidence of highly significant association with the disease. Of these, five loci harbor genes differentially expressed in patients LSG-epithelial cells. Our results show that in enriched gland-epithelial cells of pSS, both pro-apoptotic/anti-apoptotic and interferon signaling inhibition/stimulation balances may occur. Genes found over-expressed in epithelial cells are candidates for disease susceptibility.

Does genetic variation in the Delta6-desaturase promoter modify the association between alpha-linolenic acid and the prevalence of metabolic syndrome?

BACKGROUND: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are associated with protection against components of the metabolic syndrome, but the role of alpha-linolenic acid (ALA), the metabolic precursor of EPA and DHA, has not been studied. The Delta(6)-desaturase enzyme converts ALA into EPA and DHA, and genetic variation in the Delta(6)-desaturase gene (FADS2) may affect this conversion. OBJECTIVES: We hypothesize that high ALA is associated with a lower prevalence of the metabolic syndrome and that genetic variation in FADS2 modifies this association. DESIGN: We studied 1815 Costa Rican adults. Adipose tissue ALA was used as a biomarker of intake, and metabolic syndrome was identified with the definition from the National Cholesterol Education Program, Adult Treatment Panel III. Prevalence ratios (PRs) and 95% CIs were estimated from binomial regression models, and the likelihood ratio was used to test for effect modification. RESULTS: High concentrations of adipose tissue ALA were associated with lower PRs of the metabolic syndrome compared with low ALA (0.81; 95% CI: 0.66, 1.00, for the comparison between the highest and the lowest quintiles; P for trend < 0.02). Higher concentrations of adipose tissue ALA were associated with a lower PR among homozygote (0.67; 95% CI: 0.53, 0.86) and heterozygote (0.84; 95% CI: 0.72, 0.99) carriers of the FADS2 T allele, but not among homozygote carriers of the deletion variant allele (0.99; 95% CI: 0.78, 1.27; P for interaction: 0.08). CONCLUSIONS: Elevated ALA concentrations in adipose tissue are associated with lower prevalence of the metabolic syndrome. A lack of association among homozygote carriers of the FADS2 deletion allele suggests that this association may be due in part to the conversion of ALA into EPA.

Abdominal obesity and hyperglycemia mask the effect of a common APOC3 haplotype on the risk of myocardial infarction.

BACKGROUND: Plasma apolipoprotein (apo) C-III strongly predicts myocardial infarction (MI) and directly activates atherogenic processes in vascular cells. Genetic variation in the insulin response element of the APOC3 promoter is associated with an increased risk of MI. OBJECTIVE: The objective was to determine whether the APOC3 promoter variation affects plasma apo C-III concentrations and MI only when insulin sensitivity is normal. DESIGN: The APOC3*222 haplotype, defined by the minor alleles of the single nucleotide polymorphisms 3238C-->G, -455T-->C, and -482C-->T, was studied in 1703 matched nonfatal case-control pairs with MI in the Central Valley of Costa Rica. We used fasting hyperglycemia and abdominal obesity as surrogates for insulin sensitivity. RESULTS: The APOC3*222 haplotype was associated with higher apo C-III concentrations only in those with the lowest waist circumference or fasting glucose concentration. The association between the APOC3*222 haplotype and nonfatal MI, previously reported in this population, was strongly influenced by fasting hyperglycemia and abdominal obesity. The odds ratios for MI for the APOC3*222 haplotype were 1.72 (95% CI: 1.16, 2.54) and 1.84 (1.31, 2.59) in subjects in the lowest quintiles of abdominal obesity and fasting hyperglycemia, respectively, and were 0.75 (0.54, 1.05) and 1.16 (0.85, 1.59) in subjects in the highest quintiles, respectively (P for interaction <0.05). CONCLUSION: The results support the concept that mutations in the APOC3 promoter inhibit the down-regulation of APOC3 expression by insulin. This cardioprotective system becomes dysfunctional in abdominal obesity and hyperglycemia.

Ala12 variant of the peroxisome proliferator-activated receptor-gamma gene (PPARG) is associated with higher polyunsaturated fat in adipose tissue and attenuates the protective effect of polyunsaturated fat intake on the risk of myocardial infarction.

BACKGROUND: Intake of polyunsaturated fat is protective against the development of coronary heart disease. Less is known about the genetic variation modulating this association. The Ala12 allele of the peroxisome proliferator-activated receptor-gamma gene (PPARG) decreases the lipolysis of triacylglycerols in adipose tissue, which results in the accumulation of fatty acids in adipocytes. OBJECTIVE: We aimed to determine whether the Pro12Ala polymorphism interacts with polyunsaturated fat intake to affect the risk of myocardial infarction (MI). DESIGN: Cases (n = 1805) with a first nonfatal acute MI and population-based controls matched by age, sex, and area of residence (n = 1805) living in Costa Rica were genotyped for the PPARG Pro12Ala genetic polymorphism. Polyunsaturated fat intake was determined by use of a validated food-frequency questionnaire and by gas chromatography analysis of adipose tissue. Odds ratios and 95% CIs for MI were estimated by use of logistic regression. RESULTS: The relative allele frequencies of the Ala12 allele were 10% in controls and 11% in cases. Odds ratios (95% CI) for MI per each 5% increase in energy from polyunsaturated fat were 0.66 (0.53, 0.82) in Pro12/Pro12 subjects and 0.93 (0.61, 1.42) in carriers of the Ala12 allele (P for interaction = 0.03). Increments (95% CI) of polyunsaturated fat in adipose tissue per 5% increment in dietary intake were 5.4% (4.9%, 5.9%) in Pro12/Pro12 homozygotes, 6.9% (6.0%, 7.9%) in Pro12/Ala12 heterozygotes, and 7.7% (3.2%, 12.2%) in Ala12/Ala12 homozygotes (P for interaction = 0.016). CONCLUSIONS: The protective effect of polyunsaturated fat intake on MI is attenuated in carriers of the Ala12 allele of PPARG.

alpha-Linolenic acid, Delta6-desaturase gene polymorphism, and the risk of nonfatal myocardial infarction.

BACKGROUND: Delta(6)-Desaturase (FADS2) is the rate-limiting step in the polyunsaturated fatty acid (PUFA) biosynthetic pathway. OBJECTIVE: The aim was to test whether the common deletion [T/-] in the promoter of FADS2 affects the PUFA biosynthetic pathway and consequently modifies the effect of alpha-linolenic acid (ALA) on myocardial infarction (MI). DESIGN: Case subjects (n =1694) with a first nonfatal acute MI were matched by age, sex, and area of residence to 1694 population-based control subjects in Costa Rica. PUFAs were quantified by gas-liquid chromatography from plasma and adipose tissue samples. Least-squares means from generalized linear models and odds ratios (ORs) and 95% CIs from multiple conditional logistic regression models were estimated. RESULTS: The prevalence of the variant T/- allele was 48%. Eicosapentaenoic acid, gamma-linolenic acid, and arachidonic acid decreased in adipose tissue and plasma with increasing number of copies of the variant allele with a monotonic trend (P < 0.05 for all). Fasting plasma triacylglycerols by genotype were 2.08 mmol/L for TT, 2.16 mmol/L for T-, and 2.26 mmol/L for - - [ie, homozygous for the variant (deletion) allele] (P = 0.03). The FADS2 deletion was not associated with MI and did not significantly modify the association between adipose tissue ALA and the risk of MI. CONCLUSIONS: The FADS2 deletion may prevent the conversion of ALA into very-long-chain PUFAs. However, this metabolic effect is not translated into an attenuated risk between ALA and MI among carriers of the variant. It is possible that, at current intakes of ALA, any potential defect in the transcription of the gene is masked by the availability of substrate. Further research in populations deficient in ALA intake is warranted.

Effect of apolipoprotein E genotype and saturated fat intake on plasma lipids and myocardial infarction in the Central Valley of Costa Rica.

We assessed the effect of APOE polymorphisms -491 A/T, C112R (APOE*4), and R158C (APOE*2) and saturated fat intake on plasma lipid levels and risk of myocardial infarction (MI) in 1,927 case subjects and 1,927 population-based control subjects matched for age, sex, and residence, all living in the Central Valley of Costa Rica. A significant gene-diet interaction (p = 0.0157) was observed. High saturated fat intake was associated with a 49% increased risk of MI (OR = 1.49; 95% CI, 1.16-1.92) among wildtype subjects. In contrast, high saturated fat intake was associated with a 2.2-fold increased risk of MI among carriers of APOE*2 (OR = 3.17; 95% CI, 1.58-6.36) and with a 1.6-fold increase among carriers of the -491T and APOE*4 variants together (OR = 2.59; 95% CI, 1.38-4.87). Consistently, a high fat diet elicited a greater response in LDL cholesterol among carriers of APOE*2 (+ 17%) and APOE*4 (+ 14%) compared to noncarriers (+6%). The frequency of APOE variants was similar in case and control subjects, although APOE*4 homozygotes were at increased risk of MI compared to noncarriers (OR = 2.26; 95% CI, 1.03-4.98). This study supports the hypothesis that the APOE*2 and APOE*4 variants increase susceptibility to MI in the presence of high saturated fat and could explain inconsistent findings on the effects of these variants on MI in various populations.

Alcohol intake, drinking patterns, and risk of nonfatal acute myocardial infarction in Costa Rica.

BACKGROUND: Moderate alcohol consumption is associated with a lower risk of myocardial infarction (MI). Whether alcohol is truly protective or whether the amount, type, or pattern of intake is the most important is still under debate. OBJECTIVE: The purpose of this study was to determine whether alcohol intake and drinking patterns are associated with plasma lipids and the risk of MI in Costa Ricans, a population with a low intake of wine. DESIGN: We conducted a study of 2090 cases of a first nonfatal acute MI and 2090 population-based controls matched by age, sex, and residence in Costa Rica, a country with diet and lifestyles different from those of Western countries. Alcohol and dietary intakes were assessed by using validated questionnaires. RESULTS: In a multivariate conditional regression model that controlled for other cardiovascular disease risk factors, the lowest risk of MI [odds ratio (OR) = 0.44; 95% CI: 0.31, 0.61] was observed for those who drank on average 3 drinks/wk (compared with lifelong abstainers). When we looked at the frequency of consumption, we found that the risk of MI among daily drinkers (OR = 0.64; 95% CI: 0.41, 1.01) was not significantly different (P = 0.23) from that of weekend drinkers (OR = 0.76; 95% CI: 0.59, 0.98) regardless of the amount consumed. HDL cholesterol increased with the amount and frequency of alcohol intake. Similar to a few other populations, apparent protection was observed at very low alcohol intakes. CONCLUSION: Low to moderate consumption of alcohol 1-2 d/wk is independently associated with a reduced risk of MI.

APOC3/A5 haplotypes, lipid levels, and risk of myocardial infarction in the Central Valley of Costa Rica.

Genetic variation in the APOC3 and APOA5 genes has been associated with plasma triglyceride concentrations and may affect the risk of myocardial infarction (MI). To assess whether APOC3/A5 haplotypes are associated with risk of MI, we examined three single-nucleotide polymorphisms (SNPs) in APOC3 (3238C>G, -455T>C, and -482C>T) and six SNPs in the APOA5 gene (-1131T>C, c.-3A>G, c.56C>G, IVS3+476G>A, c.553G>T, and c.1259T>C) in incident cases (n = 1,703) of a first nonfatal MI matched for gender, age, and area of residence with population-based controls (n = 1,703). Conditional logistic regression models, adjusted for potential environmental confounders, were used for analysis. The common APOC3*222 haplotype was more frequent in cases than in controls (17.4% and 13.7%, respectively, P < 0.001) and was associated with increased risk of MI [odds ratio (OR) = 1.27; 95% confidence interval (95% CI), 1.09, 1.48] compared with APOC3*111 wild-type haplotype. This association was independent of the APOA5 SNPs. Although the APOC3 3238G, APOA5 -1131C, APOA5 c.-3G, and APOA5 c.1259C alleles were associated with higher triglyceride plasma concentrations, these effects could not explain the associations with MI in this population. In summary, this study supports the hypothesis that haplotypes in the APOC3 gene but not in the APOA5 gene increase susceptibility to MI.