RESUMO
Genetic variation in fatty acid desaturases (FADS) has previously been linked to long-chain polyunsaturated fatty acids (PUFAs) in adipose tissue and cardiovascular risk. The goal of our study was to test associations between six common FADS polymorphisms (rs174556, rs3834458, rs174570, rs2524299, rs174589, rs174627), intermediate cardiovascular risk factors, and non-fatal myocardial infarction (MI) in a matched population based case-control study of Costa Rican adults (n = 1756). Generalized linear models and multiple conditional logistic regression models were used to assess the associations of interest. Analyses involving intermediate cardiovascular risk factors and MI were also conducted in two replication cohorts, The Nurses' Health Study (n = 1200) and The Health Professionals Follow-Up Study (n = 1295). In the Costa Rica Study, genetic variation in the FADS cluster was associated with a robust linear decrease in adipose gamma-linolenic, arachidonic, and eicosapentaenoic fatty acids, and significant or borderline significant increases in the eicosadienoic, eicosatrienoic, and dihomo-gamma-linolenic fatty acids. However, the associations with adipose tissue fatty acids did not translate into changes in inflammatory biomarkers, blood lipids, or the risk of MI in the discovery or the replication cohorts. In conclusion, fatty acid desaturase polymorphisms impact long-chain PUFA biosynthesis, but their overall effect on cardiovascular health likely involves multiple pathways and merits further investigation.
RESUMO
BACKGROUND/OBJECTIVES: Elongases 2, 4 and 5, encoded by genes ELOVL2, ELOVL4 and ELOVL5, have a key role in the biosynthesis of very long chain polyunsaturated fatty acids (PUFAs). To date, few studies have investigated the associations between elongase polymorphisms and cardiovascular health. We investigated whether ELOVL polymorphisms are associated with adipose tissue fatty acids, serum lipids, inflammation and ultimately with nonfatal myocardial infarction (MI) in a Costa Rican population. SUBJECTS/METHODS: MI cases (n=1650) were matched to population-based controls (n=1650) on age, sex and area of residence. Generalized linear and multiple conditional logistic regression models were used to assess the associations between seven common ELOVL polymorphisms and cardiometabolic outcomes. Analyses were replicated in The Nurses' Health Study (n=1200) and The Health Professionals Follow-Up Study (n=1295). RESULTS: Variation in ELOVL2, ELOVL4 and ELOVL5 was not associated with adipose tissue fatty acids, intermediate cardiovascular risk factors or MI. In the Costa Rica study, the number of the minor allele copies at rs2294867, located in the ELOVL5 gene, was associated with an increase in total and LDL cholesterol (adjusted P-values=0.001 and <0.0001 respectively). Additionally, the number of the minor allele copies at rs761179, also located in the ELOVL5 gene, was significantly associated with an increase in total cholesterol (adjusted P-value=0.04). However, the observed associations were not replicated in independent populations. CONCLUSION: Common genetic variants in elongases are not associated with adipose tissue fatty acids, serum lipids, biomarkers of systemic inflammation, or the risk of MI.
Assuntos
Acetiltransferases/genética , Doenças Cardiovasculares/genética , Colesterol/genética , Ácidos Graxos Insaturados/genética , Inflamação/genética , Infarto do Miocárdio/genética , Polimorfismo Genético , Tecido Adiposo/metabolismo , Idoso , Alelos , Estudos de Casos e Controles , Colesterol/sangue , LDL-Colesterol/sangue , LDL-Colesterol/genética , Costa Rica , Elongases de Ácidos Graxos , Ácidos Graxos Insaturados/biossíntese , Feminino , Genótipo , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fenótipo , Fatores de RiscoRESUMO
BACKGROUND AND AIMS: Despite their relatively high content of saturated fat, studies of dairy product intake and the risk of cardiovascular disease have often yielded null or inverse results. The use of fatty acid biomarkers to reflect dairy intake could elucidate this association. This study aims to evaluate the association between dairy intake, assessed by adipose pentadecanoic (15:0) and heptadecanoic (17:0) fatty acids and food frequency questionnaire (FFQ), and the risk of nonfatal myocardial infarction (MI), in a matched case-control study of Costa Rican adults (n=3630). METHODS AND RESULTS: The association was examined using conditional logistic regression, adjusted for potential confounders. The associations of adipose tissue 15:0 and 17:0 with the risk of MI were not statistically significant (for 15:0: multivariate-adjusted OR for 5th quintile vs. 1st=1.14 (95% CI=0.85, 1.53), p-value for linear trend=0.77; for 17:0: multivariate-adjusted OR for 5th quintile vs. 1st=1.15 (95% CI=0.88, 1.51), p-value for linear trend=0.18). The association between the FFQ measure of dairy intake and MI showed evidence of a possible threshold effect, with a protective association observed for all but the top quintile of the exposure distribution. CONCLUSION: Dairy product intake as assessed by adipose tissue 15:0, 17:0, and by FFQ is not associated with a linear increase in the risk of MI in the study population. It is possible that the adverse effect of saturated fat in dairy products on cardiovascular health is offset by presence of beneficial nutrients.