The apolipoprotein A5 gene (APOA5) is a major gene that regulates lipid metabolism and is modulated by dietary factors. A novel variant rs964184 in APOA5 was identified to be associated with lipids in genome-wide association studies.
We examined whether this variant modified changes in lipid concentrations in response to a 2-y weight-loss diet intervention in a randomized trial.
The current analyses were secondary analyses of a data set from the Pounds Lost Trial. We genotyped APOA5 rs964184 in 734 overweight or obese adults who were randomly assigned to one of 4 diets that differed in percentages of energy derived from fat, protein, and carbohydrate for 2 y. We evaluated changes in fasting serum concentrations of total cholesterol (TC), LDL cholesterol, HDL cholesterol, and triglyceride from baseline to 2 y of follow-up.
After a 2-y dietary intervention, we showed significant interactions between the APOA5 rs964184 polymorphism and dietary fat intake (low compared with high) in the determination of changes in TC, LDL cholesterol, and HDL cholesterol (P-interaction = 0.007, 0.017, and 0.006, respectively). In the low-fat intake group (20% of energy derived from fat), carriers of the risk allele (G allele) exhibited greater reductions in TC and LDL cholesterol than did noncarriers (P = 0.036 and 0.039, respectively), whereas in the high-fat diet group (40% of energy derived from fat), participants with the G allele had a greater increase in HDL cholesterol than did participants without this allele (P = 0.038).
Our data showed better improvement in lipid profiles from long-term low-fat diet intake in the APOA5 rs964184 risk allele. The Pounds Lost Trial was registered at clinicaltrials.gov as NCT00072995.
[Show abstract][Hide abstract] ABSTRACT: Rates of obesity and related complex diseases such as type 2 diabetes and cardiovascular disease have climbed sharply over the past decades, in parallel with shift from principally more active lifestyle and nutritionally dense tradition diet to sedentary lifestyle and more energy-dense, Western-pattern diet. In the past few years, advances in genotyping technology and in particular a number of large-scale genome-wide association studies have made great strides in unraveling the genetic basis of complex diseases; and the growing inventory of genetic variation is facilitating efforts to investigate gene-diet interactions. Understanding gene-diet interaction has the potential to promote diet modifications on the basis of genetic makeup. Several recent large-scale studies found reproducible evidence showing consumption of sugar sweetened beverages or dietary patterns might modulate genetic predisposition to obesity or cardiovascular disease. Analyses in randomized trials also showed that genetic markers for obesity, diabetes, or cardiovascular disease might modify the metabolic response to weight-loss diets. However, little of the knowledge about gene-diet interaction has been applied in public health practice; and opinion on how genetic testing services are offered and interpreted is still divided. This review will summarize recent findings regarding obesogenic diet, genetic susceptibility, and gene-diet interactions for obesity and related complex disorders and will discuss the potential impact of these findings on public health practice.
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE
Genetic variants near IRS1 are associated with features of the metabolic syndrome (MetS). We examined whether genetic variants near IRS1 might modulate the effects of diets varying in fat content on the MetS status in a 2-year weight-loss trial.RESEARCH DESIGN AND METHODS
Two variants near IRS1, rs1522813 and rs2943641, were genotyped in 738 overweight/obese adults (age 60 ± 9 years; BMI 32.7 ± 3.9 kg/m(2)) randomly assigned to one of four weight-loss diets (a deficit of 750 kcal/day of caloric intake from baseline) varying in macronutrient contents for 2 years. We compared MetS status of high-fat (40% of caloric intake; n = 370) and low-fat (20% caloric intake; n = 368) diet groups differentiated by genotypes (rs1522813 A-allele carriers and noncarriers; rs2943641T-allele carriers and noncarriers).RESULTSAmong rs1522813 A-allele carriers, the reversion rates of the MetS were higher in high-fat diet group than those in low-fat diet group over the 2-year intervention (P = 0.002), while no significant difference between diet groups was observed among noncarriers (P = 0.27). The genetic modulation on dietary effect was independent of weight changes. The odds ratio (OR) for the 2-year reversion of the MetS was 2.88 (95% CI 1.25-6.67) comparing the high-fat and low-fat diets among rs1522813 A-allele carriers, while the corresponding OR was 0.83 (0.36-1.92) in noncarriers. The variant rs2943641 was not observed to modulate dietary effects on the MetS status.CONCLUSIONS
Our data suggest that high-fat weight-loss diets might be more effective in the management of the MetS compared with low-fat diets among individuals with A-allele of the rs1522813 variant near IRS1.
Diabetes care 09/2013; 36(11). DOI:10.2337/dc13-0018 · 8.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Several smaller studies reported interactions between dietary factors and apolipoprotein A5 (APOA5) gene polymorphisms in determination of plasma lipids. We tested interactions between APOA5 haplotypes and dietary intake in determination of plasma triglycerides (TG) and other lipids.
Participants (5487 males and females aged 45-69) were classified according to the number (0, 1, 2+) of minor APOA5 alleles (using T-1131 > C; rs662799 and Ser19 > Trp; rs3135506 polymorphisms) and into three groups of low (bottom 25%), medium (26th-75th percentile) and high (top 25%) of intake of total energy and total, saturated and polyunsaturated fats, assessed by food frequency questionnaire. The age-sex adjusted geometric means of plasma TG increased with the number of minor alleles, from 1.57 (standard error 0.01), to 1.79 (0.02) to 2.29 (0.10) mmol/L (p < 0.00001) but TG did not differ between groups with low, medium and high total energy intake (p = 0.251). TG concentrations were highest in subjects with the combination of 2+ minor alleles and the highest energy intake (mean 2.59 [0.19], compared with 1.62 [0.03] in subjects with lowest energy intake and no minor allele) but the interaction between energy intake and APOA5 haplotypes was not statistically significant (p = 0.186). Analogous analyses with total, saturated and polyunsaturated fat intake yielded similar nonsignificant results. Effects of APOA5 and dietary intakes on total and HDL cholesterol were weaker and no interactions were significant.
In this Slavic Caucasian population sample, we did not detect the hypothesized interaction between common SNPs within the APOA5 gene and diet in determination of blood lipids.
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