Features of the metabolic syndrome are modulated by an interaction between the peroxisome proliferator-activated receptor-delta −87T>C polymorphism and dietary fat in French-Canadians

Abstract

The metabolic syndrome (MS) is influenced by genetic and environmental factors. Peroxisome proliferator-activated receptor delta (PPAR-delta), a transcription factor involved in lipid metabolism, is a candidate gene for the MS. Objective: We verified whether genetic variants in this gene are associated with the MS and whether dietary fatty acids interact with the À87T4C polymorphism. Methods: By direct sequencing, we identified 15 variants in the PPAR-delta gene and analyses were pursued with the À87T4C polymorphism for 340 subjects. Results: Metabolic variables were comparable among each genotype group. The À87T4C polymorphism, fat intake and the interaction accounted, respectively for 2.2, 1.9 and 1.5% of the variance in high-density lipoprotein cholesterol (HDL-C) levels (Po0.05) (age, sex and energy intake were included into the model). The total cholesterol/HDL-C ratio was also modulated by a gene-diet interaction and by the -87T4C polymorphism (Po0.05). No gene-diet interaction effects were observed for other features of the MS. The age-and sex-adjusted odds ratio (OR) of exhibiting three or more features of the MS when carrying the À87C allele was 0.62 (P ¼ 0.04) compared to -87T/T. However, in subjects consuming less than 34.4% of energy from fat (median of fat consumption), the OR in carriers of the À87C allele was of 0.42 (P ¼ 0.008). Conclusion: These data suggest that the PPAR-delta À87T4C polymorphism may be associated with a lower risk to exhibit the MS and this association is influenced by dietary fat intake.

Variation in the peroxisome proliferator-activated receptor δ gene in relation to common metabolic traits in 7,495 middle-aged white people

“…The minor allele of the rs2016520 variant in exon 4 has inconsistently been associated with decreased fasting levels of HDL-cholesterol [15], increased LDL-cholesterol a Regression estimate±SE of the logarithm of HOMA-IR (pmol/l×mmol/l) with haplotype 1 (A-C) as base Haplotype frequencies were estimated using the EM algorithm and association with quantitative traits was evaluated by global and haplotypespecific score statistics ( p value) and simulation (p SIM ) [31] Estimates of the effect sizes of each haplotype were estimated by modelling the haplotype×phenotype interaction [32] [16,17] and increased fasting plasma glucose [37] or decreased BMI [20], even though some studies found no association [19,21]. Yet all studies were probably statistically underpowered, involving fewer than 1,000 participants.…”

“…Previous studies of the variation in PPARD in relation to features of the metabolic syndrome have resulted in conflicting results. Several studies including fewer than 1,000 participants have investigated the c. −87T→C (rs2016520) variant in exon 4 in relation to serum lipid profiles and have shown a positive association of the minor C allele with higher serum levels of LDL-cholesterol [15], lower HDL-cholesterol [16,17], higher triacylglycerol [18] or no association [19][20][21]. In addition, a recent paper reported that three variants in PPARD and a haplogenotype of these variants were associated with increased insulinstimulated whole-body and skeletal muscle glucose uptake in a study including 129 carefully phenotyped subjects [22].…”

Retinoid X Receptor Heterodimer Variants and Cardiovascular Risk Factors

“…This C allele of c.-87T C polymorphism was also shown to be associated with unfavorable phenotypes, such as low HDL-C in women 117) , and increased fasting plasma glucose 118,119) . On the other hand, from the analysis of 15 PPAR polymorphisms among subjects without type 2 diabetes or hereditary dyslipidemia in French-Canadians, only the C allele of c.-87T C showed an association with favorable phenotypes, such as a lower risk of metabolic syndrome 120) , and lower BMI, the latter of which was reported in another Caucasian group 121) . From the standpoint of individual differences in responsiveness to 20 weeks of endurance exercise training, the C allele of -87T C was associated not only with smaller training-induced increase in maximal oxygen consumption and lower training response in maximal power output, but also with a greater increase in plasma HDL-C with physical training (HERITAGE Family Study) 122) .…”

Study on the Effects of PPARG and PPAR-B/D Gene Variations on Serum LDL Subfractions in Patients with Coronary Heart Disease

“…13,[29][30][31][32][33] Ancak bazı çalışma sonuçları çelişkilidir. [34][35][36] PPAR-B/D +294T/C minör C allelinin yüksek HDL-K düzey-leri ile ilişkili olduğunu ya da serum lipid düzeyle-rine etkisiz olduğunu öne süren çalışmalar da mevcuttur. [34][35][36] Son çalışmalarda, PPAR-B/D agonisti MBX-8025'in lipoprotein alt fraksiyonları üzerinde etki göstererek aterojenik dislipidemi tedavisinde statin tedavisine komplementer olumlu iyileşme sağla-dığı bildirilmiştir.…”

“…[34][35][36] PPAR-B/D +294T/C minör C allelinin yüksek HDL-K düzey-leri ile ilişkili olduğunu ya da serum lipid düzeyle-rine etkisiz olduğunu öne süren çalışmalar da mevcuttur. [34][35][36] Son çalışmalarda, PPAR-B/D agonisti MBX-8025'in lipoprotein alt fraksiyonları üzerinde etki göstererek aterojenik dislipidemi tedavisinde statin tedavisine komplementer olumlu iyileşme sağla-dığı bildirilmiştir. 37 Fakat literatürde PPAR-B/D +294T/C varyasyonunun serum lipoprotein alt fraksiyonları üzerindeki etkilerini inceleyen bir araştırma bulunmamaktadır.…”