ABSTRACT
BACKGROUND: The degree of fatty acid (FA) unsaturation as a determinant of lipid peroxidation has been inadequately studied. METHODS: We examined associations of plasma free F2α-isoprostanes (F2-IsoPs), an indicator of in-vivo lipid peroxidation, with the levels/intake of FAs, adjusted for the risk factors of cardiovascular disease (CVD) in 1211 Finnish men and women, of whom 50% were hypertensive, aged 59.3 ± 8.3 years, mean ± SD. RESULTS: Elevated age- and sex-adjusted plasma free levels of omega-6 and omega-3 polyunsaturated Fas (PUFAs), saturated FAs (SFAs), and the PUFA/SFA and the omega-6/omega-3 PUFA ratios were all associated with decreased F2-IsoPs. High dietary SFA intake was associated with elevated F2-IsoP concentrations. In a multivariable regression (with clinical, nutritional, and behavioral CVD risk factors), female gender, body mass index (BMI), serum apolipoprotein A1, and NT-proBNP (natriuretic peptide) were positively associated with the F2-IsoPs, whereas the dietary PUFA/SFA ratio, plasma ß-carotene, the omega-6/omega-3 PUFA ratio, and protein intake showed inverse associations. CONCLUSIONS: We propose that elevated lipid peroxidation is associated with several risk factors of CVD, such as a low PUFA/SFA ratio, whereas the FA precursors of lipid peroxidation, i.e. omega-3 and omega-6 PUFAs are associated with attenuated F2-IsoP levels. These findings provide mechanistic support for earlier observations linking PUFA to improved cardiovascular health.
Subject(s)
Cardiovascular Diseases/etiology , Fatty Acids/blood , Hypertension/blood , Lipid Peroxidation , Adult , Aged , Aged, 80 and over , Cardiovascular Diseases/epidemiology , Cross-Sectional Studies , Dietary Fats/administration & dosage , F2-Isoprostanes/blood , Fatty Acids, Omega-3/blood , Fatty Acids, Omega-6/blood , Female , Finland , Humans , Hypertension/physiopathology , Male , Middle Aged , Multivariate Analysis , Regression Analysis , Retrospective Studies , Risk FactorsABSTRACT
Type 2 diabetes (T2D) is a common, polygenic chronic disease with high heritability. The purpose of this whole-genome association study was to discover novel T2D-associated genes. We genotyped 500 familial cases and 497 controls with >300,000 HapMap-derived tagging single-nucleotide-polymorphism (SNP) markers. When a stringent statistical correction for multiple testing was used, the only significant SNP was at TCF7L2, which has already been discovered and confirmed as a T2D-susceptibility gene. For a replication study, we selected 10 SNPs in six chromosomal regions with the strongest association (singly or as part of a haplotype) for retesting in an independent case-control set including 2,573 T2D cases and 2,776 controls. The most significant replicated result was found at the AHI1-LOC441171 gene region.
