L162V Polymorphism Research Articles

The Correlation Between Peroxisome Proliferator-Activated Receptor Alpha and Gamma Polymorphisms and Acute Coronary Syndrome.

Objective: This study aims to evaluate the relationship between peroxisome proliferator-activated receptor (PPAR) alpha and gamma gene polymorphisms and acute coronary syndrome (ACS) clinically.Subject and methods: Peripheral blood samples were collected from a total of 200 people, including 100 acute coronary syndrome patients and 100 controls aged 19 to 93 years, admitted to the Pamukkale University Emergency Medicine Department. The healthy volunteers had no known chronic or acute diseases, no history of drug use, and no recent history of coronary artery disease (CAD). PPAR alpha L162V and PPAR gamma C161T gene polymorphic regions were detected using DNA sequencing analyses. In addition, data collected from the hemogram and biochemical parameters and comorbidities of the patients were statistically analyzed.Results: PPAR gamma C161T polymorphisms were compared between groups. The CT heterozygous rate in the patient group (74%) was higher than in the control group (7%). The T allele was more common in the patient group (0.37) compared to the control group (0.03). When PPAR alpha L162V polymorphism was compared, VV homozygous individuals were %19 in the patient group and none in the control group. The V allele was found to be statistically higher in patients with ACS (p<0.01).Conclusion: The findings revealed that elevated PPAR alpha L162V and PPAR gamma C161T gene polymorphisms were associated with a progressive risk of ACS.

L162v Polymorphism of Par-Α Gene, A603g Polymorphism of Tissue Factor Gene and Risk of Coronary Heart Disease in Russian Population

Purpose The goal of this study is to determine the association of L162V polymorphism of PPAR-alpha gene, A603G polymorphism of tissue factor gene and the risk of coronary heart disease development in Russian population. Materials and Methods A clinical and genetic study of 414 patients with CHD and 220 people of comparable age without CHD which amounted to a control group was performed. L162L and L162V genotypes of L162V polymorphism of PPAR-α gene, A603A, A603G and G603G genotypes of A603G polymorphism of tissue factor gene were determined by polymerase chain reaction followed by restriction analysis. Results A carriage of L162V genotype and V allele of PPAR-α gene was associated with an increase risk of CHD in 2,13 times (L162V genotype) and in 2,21 times (V allele), with an increase in risk of CHD before the age of 45 years in 4,68 times (L162V genotype) and in 3,88 times (V allele). Significantly higher in patients with CHD compared with the general population and in patients with a carriage of G603G genotype and G allele of tissue factor gene was associated with the increase of CHD risk in 2,68 times (G603G genotype) and in 4,37 times (G allele), occurred more frequently in patients with debut of disease at age of 45 years and younger. The level of tissue factor was significantly higher in patients with CHD – carriers G603G genotype compared with carriers A603A genotype (217,9±15,2 pg/ml and 152,6±30,4 pg/ml, respectively, p=0,04). A carriage of the combination of L162V and G603G genotypes was associated with an increased risk of CHD in 3,04 times. Conclusion A carriage of V allele of L162V polymorphism of PPAR-α gene and G allele of A603G polymorphism of tissue factor gene, as well as their pair combination are associated with an increased CHD risk, especially at age 45 years or less.

L162v Polymorphism of Peroxisome Proliferator-activated Receptor-alpha Gene and Markers of Immune Inflammation in Patients with Coronary Artery Disease

New risk factors for coronary artery disease (CAD) have been identified recently – mediators of immune inflammation. Peroxisome proliferator-activated receptors alpha (PPAR-α) belong to nuclear receptors superfamily and regulate the activity of different genes coding the factors of immune inflammation. The goal of this study is to determine the association of L162V polymorphism of PPAR-α gene with factors of immune inflammation and the risk of coronary artery disease development in Russian population. The current study included 424 patients with coronary artery disease (359 men and 65 women) aged 33 to 80 years (mean age- 61,6 ± 0,48 years). The control group consisted of 220 people without CAD of comparable age (mean age- 60,09 ± 0,72 years, p = 0.081). Polymerase chain reaction and restriction analysis were performed. IL-6, interferon-gamma (IF-γ) and tumor necrosis factor-alpha (TNF-α) levels of blood plasma were tested by Elisa. The frequency of L162V genotype of PPAR-α gene in coronary artery disease patients was higher than in control group (14,0% and 6,4% respectively, p=0.004). No significant differences in L162L and L162V genotype distribution in CAD patients with or without arterial hypertension, abdominal obesity, diabetes type2, smoking factor, family history were revealed. In CAD patients with the debut of the disease at the age of 45 and younger the frequency of L162V genotype was higher than in the subgroup of patients with the disease progress at age 46-59 years and (OR=4,68; CI:2,3÷9,52). The level of interleukin 6 was significantly higher in patients with CAD - L162V genotype carriers compared to L162L genotype carriers (37,5 ± 8,3 pg/ml and 9,2 ± 3,5 pg/ml respectively, p = 0.0006). The levels of TNF—α and IF-γ were significantly higher in patients with CAD - L162V genotype carriers compared with L162L genotype carriers. The study has demonstrated that 162V PPARα allelic variant influence the predisposition for CAD in human subjects, probably mediated by modulation of the proinflammatory cytokines profile. L162V genotype and V162 allele of PPAR-α gene was associated with the risk of coronary artery disease debut at the age 45 years and younger.

Effects of Plasma Phospholipid Fatty Acid Composition and PPAR‐alpha L162V Polymorphism on C‐reactive Protein Levels in Response to an n‐3 Fatty Acid Supplementation

Background Fish-oil derived fatty acids (FAs) of the n-3 family including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) reduce inflammation through several underlying mechanisms including altered phospholipids FA composition. The L162V polymorphism of the PPAR-α gene is associated with a deteriorated metabolic profile and with obesity indices in numerous studies. Objective: To study whether the PPAR-α L162V polymorphism and changes in plasma phospholipid FA composition influence plasma C-reactive protein (CRP) levels in healthy adults following the n-3 FA supplementation. Method: 189 subjects were supplemented daily with 3g of n-3 FAs (1.9-2.2g EPA and 1.1g DHA) during six weeks. Changes in CRP levels are defined by Δ CRP and changes in plasma phospholipids n-3 (EPA+DHA) by Δ n-3. Results: In univariate analyses, Δ n-3 was negatively correlated with Δ CRP (r=-0.17 p=0.02). After stratification for sex, correlations were stronger in men (r=-0.24 p=0.02) and no longer significant in women (r=-0.11 p=0.31). In multiple linear regression analyses including age, sex, BMI, and hormonal contraceptives as independent variables, Δ n-3 (3.65% p= 0.01) and PPAR-α L162V (2.10% p= 0.04) were the strongest correlates of Δ CRP. Conclusions These results suggest that the incorporation of n-3 FAs in plasma phospholipids and PPAR-α L162V polymorphism may contribute to changes in plasma CRP levels in response to an n-3 FA supplementation. Funding provided by CIHR Operating Grant.

PPARα-L162V polymorphism is not associated with schizophrenia risk in a Croatian population

Disturbances of lipid and glucose metabolism have been repeatedly reported in schizophrenia. A functional L162V polymorphism in peroxisome proliferator-activated receptor alpha (PPARα) gene has been extensively investigated in etiology of abnormal lipid and glucose metabolism, yet not in schizophrenia. We determined whether the schizophrenia risk was associated with L162V polymorphism and we examined the impact of L162V variant on age of onset, and data of psychopathology scores. We also hypothesized that plasma glucose and lipid concentrations in patients may be influenced by L162V polymorphism. Genotype and allele frequencies between 203 patients and 191 controls did not differ significantly. Females heterozygous for the PPARα genotype (L162V) manifested significantly lower negative symptom scores, tended toward an earlier onset, and had significantly greater triglyceride levels. The PPARα-L162V polymorphism is not associated with schizophrenia risk in Croatian population, but it impacts clinical expression of the illness and plasma lipid concentrations in female patients.

L162V polymorphism of ppar-alfa gene, coronary arteries and cardiac remodeling in patients with coronary heart disease

L162V polymorphism of ppar-alfa gene, coronary arteries and cardiac remodeling in patients with coronary heart disease

Lipoprotein Lipase and PPAR Alpha Gene Polymorphisms, Increased Very-Low-Density Lipoprotein Levels, and Decreased High-Density Lipoprotein Levels as Risk Markers for the Development of Visceral Leishmaniasis byLeishmania infantum

In visceral leishmaniasis (VL) endemic areas, a minority of infected individuals progress to disease since most of them develop protective immunity. Therefore, we investigated the risk markers of VL within nonimmune sector. Analyzing infected symptomatic and, asymptomatic, and noninfected individuals, VL patients presented with reduced high-density lipoprotein cholesterol (HDL-C), elevated triacylglycerol (TAG), and elevated very-low-density lipoprotein cholesterol (VLDL-C) levels. A polymorphism analysis of the lipoprotein lipase (LPL) gene using HindIII restriction digestion (N = 156 samples) (H+ = the presence and H− = the absence of mutation) revealed an increased adjusted odds ratio (OR) of VL versus noninfected individuals when the H+/H+ was compared with the H−/H− genotype (OR = 21.3; 95% CI = 2.32–3335.3; P = 0.003). The H+/H+ genotype and the H+ allele were associated with elevated VLDL-C and TAG levels (P < 0.05) and reduced HDL-C levels (P < 0.05). An analysis of the L162V polymorphism in the peroxisome proliferator-activated receptor alpha (PPARα) gene (n = 248) revealed an increased adjusted OR when the Leu/Val was compared with the Leu/Leu genotype (OR = 8.77; 95% CI = 1.41–78.70; P = 0.014). High TAG (P = 0.021) and VLDL-C (P = 0.023) levels were associated with susceptibility to VL, whereas low HDL (P = 0.006) levels with resistance to infection. The mutated LPL and the PPARα Leu/Val genotypes may be considered risk markers for the development of VL.

L162V polymorphism of peroxisome proliferator-activated receptor-alpha gene and markers of endothelial dysfunction in coronary heart disease patients in Russia

L162V polymorphism of peroxisome proliferator-activated receptor-alpha gene and markers of endothelial dysfunction in coronary heart disease patients in Russia

Different effects of PPARA, PPARG and ApoE SNPs on serum lipids in patients with coronary heart disease based on the presence of diabetes

BackgroundThe aim of this study was to investigate the individual or combined effects of PPARA-L162V, PPARG-C161T and APOE polymorphisms on hyperlipidemia in coronary heart disease (CHD) patients. MethodsOur study included 223 patients with CHD (103 with type 2 diabetes (T2DM), 120 without diabetes) and 101 controls. All genotypes were determined by PCR–RFLP technique. ResultsGenotypic and allelic distributions of PPARA-L162V polymorphism were similar between study and control groups (p>0.05). The serum total-cholesterol (TC) and LDL-cholesterol (LDL-C) levels were higher in PPARA-V162 allele carriers in non-diabetic CHD patients (p=0.007 and p=0.038, respectively). The increasing effect of the PPARA-V162 allele on serum TC and LDL-C levels was weakened with the presence of PPARG-161T allele in the non-diabetic CHD patients. The ApoE4–PPARA-V162 allelic combination of the ApoE/PPARA genes was found to be more frequent in diabetic CHD patients independent of serum lipids (p=0.035). ConclusionsThe PPARA V162 allele has an increasing effect on TC and LDL-C levels and this effect was reduced by carrying PPARG T161 allele in non-diabetic CHD patients. On the other hand, the V162 allele may be associated with an increased risk of CHD in diabetic CHD patients due to the presence of ApoE4 allele independent of serum lipids. We suggest that the PPARA L162V polymorphism may have diverse effects on serum lipids and CHD risk depends on the presence of T2DM.

Association of the peroxisome proliferator-activated receptor α gene L162V polymorphism with stage C heart failure

To analyze whether genetic variants of PPARA are associated with the development of stage C heart failure. We analyzed the distribution of the rs1800206, rs4253778 and rs135551 polymorphisms in genomic DNA extracted from peripheral blood cells of 534 patients in different heart failure stages and 63 healthy individuals. The mRNA expression of the peroxisome proliferator-activated receptor (PPAR)α target genes long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) and medium-chain acyl-CoA dehydrogenase (MCAD) was measured in myocardial biopsies of a subgroup of stage B and C patients. Functional studies were performed in HL-1 cardiomyocytes. The V162 allele of the rs1800206 polymorphism was more frequent in stage C patients than in stage A and B patients and healthy individuals. Patients with the V162 allele exhibited decreased myocardial LCHAD and MCAD mRNA expression as compared to L162 homozygote patients. In addition, stage C patients exhibited lower myocardial LCHAD and MCAD mRNA expression than stage B patients. Cardiomyocytes transfected with the V162 allele presented decreased PPARα transcriptional activity, LCHAD mRNA expression and ATP production compared to cardiomyocytes transfected with the L162 variant. These findings suggest that the V162 allele of the human PPARA gene can be a new risk factor in the development of stage C heart failure, likely via depressed cardiac PPARα activity.

Effects of Peroxisome Proliferator-Activated Receptors, Dietary Fat Intakes and Gene–Diet Interactions on Peak Particle Diameters of Low-Density Lipoproteins

The risk of cardiovascular diseases (CVDs) is modulated by gene–diet interactions. The objective of this study was to examine whether gene–diet interactions affect peak particle diameters (PPD) of low-density lipoprotein (LDL). Methods: The study included 674 participants. A food frequency questionnaire was administered to obtain dietary information. LDL-PPD was determined by non-denaturing 2–16% polyacrylamide gradient gel electrophoresis. Peroxisome proliferator-activated receptor (PPAR) gene polymorphisms PPARα L162V (rs1800206), PPARγ P12A (rs1801282) and PPARδ –87T→C (rs2016520) were determined by PCR-RFLP. Results: Among carriers of thePPARα L162V polymorphism, gene–diet interaction effects on LDL-PPD were observed with saturated fat (p = 0.0005) and total dietary fat (p = 0.006). Among PPARα V162 carriers, subjects with higher saturated fat intakes had smaller LDL-PPD than those with lower intakes (254.23 ± 2.74 vs. 256.21 ± 2.61 Å, respectively, p = 0.007). Among subjects homozygous for the PPARα L162 allele, those with higher saturated fat intakes had larger LDL-PPD than those with lower saturated fat intakes (255.86 ± 2.66 vs. 255.05 ± 2.65 Å, respectively, p = 0.01). Gene–diet interactions were also found for PPARγ P12A polymorphism with saturated fat intake (p = 0.04) and for PPARδ –87T→C with the polyunsaturated/saturated fat ratio (p = 0.0013). Conclusions: These results stress that dietary factors should be included in studies determining the effect of different polymorphisms on CVD risk factors.

PPARα L162V polymorphism alters the potential of n‐3 fatty acids to increase lipoprotein lipase activity

Omega-3 fatty acids (FAs) may accelerate plasma triglyceride (TG) clearance by altering lipoprotein lipase (LPL) activity. Yet, the ability of n-3 FAs to increase LPL activity is dependent on transcription factors such as peroxisome proliferator-activated receptor alpha (PPARalpha). The objective was to examine the effects of n-3 FAs on LPL activity considering the occurrence of PPARalpha L162V polymorphism. First, 14 pairs of men either L162 homozygotes or carriers of the V162 allele were supplemented with n-3 FAs. Second, transient transfections in HepG2 cells, for the L162- and V162-PPARalpha variants with the peroxisome proliferator-response element from the human LPL gene, were transactivated with n-3 FAs. In vivo results demonstrate that the LPL activity increased non-significantly by 14.4% in L162 homozygotes compared with 6.6% in carriers of the PPARalpha-V162 allele, after n-3 FA supplementation. Additionally, the L162 homozygotes tended towards an inverse correlation between LPL activities and plasma TG levels. Conversely, carriers of the V162 allele showed no such relationship. In vitro data demonstrates that transcription rates of LPL tended to be higher for the L162-PPARalpha than V162-PPARalpha after n-3 FAs activation. Overall, these results indicate that n-3 FA supplementation increases the transcription rate of LPL to a greater extent in L162-PPARalpha than V162-PPARalpha.

Omega-3 fatty acids regulate gene expression levels differently in subjects carrying the PPARα L162V polymorphism

Omega-3 fatty acids (FAs) are natural ligands of the peroxisome proliferator-activated receptor-alpha (PPARalpha), a nuclear receptor that modulates expression levels of genes involved in lipid metabolism. The L162V polymorphism of the PPARalpha gene is associated with a deteriorated metabolic profile. We postulate that subjects carrying the PPARalpha-V162 allele exhibit differences in the expression of PPARalpha and its target genes after incubation with omega-3 FAs compared with L162 homozygotes. Peripheral blood monocytes from six men carrying the PPARalpha-V162 allele paired for age and for body mass index with six L162 homozygotes were differentiated into macrophages and activated with eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or mixtures of EPA:DHA. Data demonstrates that gene expression levels of PPARalpha and apolipoprotein AI (APOA1) were significantly lower for carriers of the PPARalpha-V162 allele compared to L162 homozygotes after the addition of DHA and a mixture of EPA:DHA. Additionally, lipoprotein lipase (LPL) gene expression displayed a tendency to be lower in the PPARalpha L162V polymorphism subgroup after the addition of a mixture of EPA:DHA. Consequently, individuals carrying the PPARalpha-V162 allele may demonstrate inferior improvements in their lipid profile due to alterations in gene expression rates in response to omega-3 FA supplementation.

Plasman-3 fatty acid response to ann-3 fatty acid supplement is modulated by apoE ɛ4 but not by the common PPAR-α L162V polymorphism in men

The risk of Alzheimer's disease is increased for carriers of apoE4 (E4) or the PPAR-alpha L162V polymorphism (L162V), but it is decreased in fish and seafood consumers. The link between high fish intake and reduced risk of cognitive decline in the elderly appears not to hold in carriers of E4, possibly because better cognition is linked to EPA+DHA in the blood, but only in non-carriers of E4. As yet, no such studies exist in carriers of L162V. Our objective was to determine whether the plasma fatty acid response to a dietary supplement of EPA+DHA was altered in carriers of L162V and/or E4. This was an add-on project; in the original study, men were selected based on whether or not they were carriers of L162V (n 14 per group). E4 status was determined afterwards. All subjects received an EPA+DHA supplement for 6 weeks. L162V polymorphism did not interact with the supplement in a way to alter EPA and DHA incorporation into plasma lipids. However, when the groups were separated based on the presence of E4, baseline EPA and DHA in plasma TAG were 67 and 60 % higher, respectively, in E4 carriers. After the supplementation, there were significant gene x diet interactions in which only non-carriers had increased EPA and DHA in plasma NEFA and TAG, respectively.

Omega‐3 fatty acids regulate gene expression levels differently in macrophages of men carrying the PPARα‐L162V polymorphism

Omega‐3 fatty acids (FAs) are natural ligands of the peroxisome proliferator‐activated receptor‐α (PPARα), a nuclear receptor that modulates expression levels of genes involved in lipid metabolism. The L162V polymorphism located in the ligand binding domain of the PPARα gene is associated with a deteriorated plasma lipid profile. Therefore, we postulate that subjects carrying the V162 allele exhibit differences in the activation of PPARα and its target genes after incubation with omega‐3 FAs compared with L162 homozygotes. Peripheral blood monocytes from 6 men carrying the V162 allele paired for age and for body mass index with 6 L162 homozygotes were differentiated into macrophages and incubated with eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or mixtures of EPA: DHA. Results demonstrate that gene expression levels of PPARα and apolipoprotein AI were significantly lower for carriers of the V162 allele compared to L162 homozygotes after the addition of DHA and a mixture of EPA: DHA. Additionally, lipoprotein lipase expression displayed a tendency to be lower in carriers of the V162 allele after the addition of a mixture of EPA: DHA. Consequently, subjects bearing the PPARα V162 allele may demonstrate inferior improvements in the plasma lipid profile due to lower PPARα and its target genes expression rates in response to omega‐3 FA supplementation. Funding provided by a CIHR Operating Grant.

Diet-gene interactions between dietary fat intake and common polymorphisms in determining lipid metabolism

Current dietary guidelines for fat intake have not taken into consideration the possible genetic differences underlying the individual variability in responsiveness to dietary components. Genetic variability has been identified in humans for all the known lipid metabolim-related genes resulting in a plethora of candidate genes and genetic variants to examine in diet-gene interaction studies focused on fat consumption. Some examples of fat-gene interaction are reviewed. These include: the interaction between total intake and the 514C/T in the hepatic lipase gene promoter in determining high-density lipoprotein cholesterol (HDL-C) metabolism; the interaction between polyunsaturated fatty acids (PUFA) and the 75G/A polymorphism in the APOA1 gene plasma HDL-C concentrations; the interaction between PUFA and the L162V polymorphism in the PPARA gene in determining triglycerides and APOC3 concentrations; and the interaction between PUFA intake and the 1131TC in the APOA5 gene in determining triglyceride metabolism. Although hundreds of diet-gene interaction studies in lipid metabolism have been published, the level of evidence to make specific nutritional recommendations to the population is still low and more research in nutrigenetics has to be undertaken.

The L162V Polymorphism of the Peroxisome Proliferator Activated Receptor Alpha Gene (PPARA) is not Associated with Type 2 Diabetes, BMI or Body Fat Composition

The L162V single nucleotide polymorphism in PPARA is suggested to play an important role in the pathogenesis of type 2 diabetes, obesity, and body fat composition. However, clinical evidence is controversial. Our aim was to investigate the relationships of the L162V SNP with type 2 diabetes, pre-diabetes phenotypes, adiposity, and plasma lipid levels. In addition, we studied the associations of the L162V SNP with body fat composition, intramyocellular lipids, and liver fat content. Furthermore, we examined if the L162V SNP was associated with changes in BMI, insulin secretion, insulin resistance, body fat composition, intramyocellular lipids, and liver fat content in response to lifestyle intervention. Data from two large cross sectional studies, the combined TULIP/TUEF cohorts, and the LURIC study were analysed. Prospective data were obtained from TULIP participants who underwent a lifestyle intervention. A total of 4,779 subjects were studied. BMI was measured in all subjects. Type 2 diabetes was diagnosed in a subgroup of the LURIC study. In the TULIP study total body fat, non-visceral adipose tissue, and visceral adipose tissue were measured with magnetic resonance tomography. Liver fat and intramyocellular lipid content were quantified with (1)H magnetic resonance spectroscopy. Insulin sensitivity and insulin secretion were estimated from oral glucose tolerance testing. The L162V SNP was neither associated with type 2 diabetes or BMI nor with body fat composition, intramyocellular lipids or liver fat content. According to our study, the L162V SNP does not have a strong impact on the pathogenesis of type 2 diabetes or obesity.

PPAR-α L162V and PGC-1 G482S gene polymorphisms, but not PPAR-γ P12A, are associated with alcohol consumption in a Spanish Mediterranean population

Background Peroxisome Proliferator-Activated Receptors (PPARs) and its co-activators are regulatory elements of the cellular lipid homeostasis and have been associated with feeding behavior modulation. Animal models suggest that these genes may be involved in alcohol consumption regulation. However, no studies in humans exist. Our aim is to estimate the possible association between polymorphisms in the PPAR-α, PPAR-γ and PPAR-γ co-activator 1A ( PGC-1A) genes and alcohol consumption in humans. Methods We have conducted a cross-sectional study between the PPAR-α L162V, PPAR-γ P12A and PGC-1A G482S polymorphisms, and alcohol consumption in a general Mediterranean Spanish population (303 men and 443 women). Results We have found an association between the L162V polymorphism and alcohol consumption in which, carriers of the V allele were more prevalent among alcohol consumers (19.4% vs. 9.8%; OR 2.69; 95% CI: 1.31–5.54, p = 0.007). The G482S polymorphism showed a significantly higher frequency in the group of high alcohol drinkers than in non-high alcohol drinkers (33.4% vs. 20.6%; OR 2.28; 95% CI: 1.07–4.88, p = 0.034). Mean alcohol consumption was higher as the number of G alleles increased (GG 8.6 ± 12.8 g/day, GS 6.6 ± 9.2 g/day, SS 5.6 ± 7.8 g/day, p = 0.003). These results remained statistically significant after covariate adjustment. Conclusions PPAR-α L162V and PGC-1A G482S polymorphisms are associated with alcohol consumption in the Mediterranean population.

Effect of the PPAR-Alpha L162V Polymorphism on the Cardiovascular Disease Risk Factor in Response to n–3 Polyunsaturated Fatty Acids

Background: Dietary n–3 polyunsaturated fatty acids (PUFAs) decrease the risk of cardiovascular disease (CVD). Yet, genetic variations of the gene encoding the peroxisome proliferator-activated receptor-α (PPARα) can also modulate CVD risk factors. Since fatty acids, including n–3 PUFAs, are natural ligands of PPARα, a gene-diet interaction effect could be observed. Aims: To examine whether n–3 PUFA- induced changes in CVD risk factors are influenced by the PPARα L162V polymorphism. Methods: Fourteen men, carriers of the V162 allele and 14 L162 homozygotes, were matched according to age and body mass index. Subjects followed, for 8 weeks, a low-fat diet and then were supplemented daily with 5 g of fish oil for 6 weeks. Results: Baseline characteristics were similar for both genotype groups. Independently of the genotype, the supplementation was associated with a significant decrease in plasma triacylglycerol and fasting glucose concentrations, diastolic blood pressure, and with an increase in total apolipoprotein B concentrations. The extent of the decrease in plasma triacylglycerol concentrations was comparable for both genotype groups (p < 0.03). A significant genotype-by-diet interaction effect was observed for plasma C-reactive protein concentrations (p = 0.01). Conclusions: The PPARα L162V polymorphism may contribute to the interindividual variability in the CVD risk factor response to n–3 PUFAs.

PPARα L162V underlies variation in serum triglycerides and subcutaneous fat volume in young males

BackgroundOf the five sub-phenotypes defining metabolic syndrome, all are known to have strong genetic components (typically 50–80% of population variation). Studies defining genetic predispositions have typically focused on older populations with metabolic syndrome and/or type 2 diabetes. We hypothesized that the study of younger populations would mitigate many confounding variables, and allow us to better define genetic predisposition loci for metabolic syndrome.MethodsWe studied 610 young adult volunteers (average age 24 yrs) for metabolic syndrome markers, and volumetric MRI of upper arm muscle, bone, and fat pre- and post-unilateral resistance training.ResultsWe found the PPARα L162V polymorphism to be a strong determinant of serum triglyceride levels in young White males, where carriers of the V allele showed 78% increase in triglycerides relative to L homozygotes (LL = 116 ± 11 mg/dL, LV = 208 ± 30 mg/dL; p = 0.004). Men with the V allele showed lower HDL (LL = 42 ± 1 mg/dL, LV = 34 ± 2 mg/dL; p = 0.001), but women did not. Subcutaneous fat volume was higher in males carrying the V allele, however, exercise training increased fat volume of the untrained arm in V carriers, while LL genotypes significantly decreased in fat volume (LL = -1,707 ± 21 mm3, LV = 17,617 ± 58 mm3 ; p = 0.002), indicating a systemic effect of the V allele on adiposity after unilateral training. Our study suggests that the primary effect of PPARα L162V is on serum triglycerides, with downstream effects on adiposity and response to training.ConclusionOur results on association of PPARα and triglycerides in males showed a much larger effect of the V allele than previously reported in older and less healthy populations. Specifically, we showed the V allele to increase triglycerides by 78% (p = 0.004), and this single polymorphism accounted for 3.8% of all variation in serum triglycerides in males (p = 0.0037).