Dataset Information

Genetic variants at the PDZ-interacting domain of the scavenger receptor class B type I interact with diet to influence the risk of metabolic syndrome in obese men and women.

ABSTRACT: The scaffolding protein PDZ domain containing 1 (PDZK1) regulates the HDL receptor scavenger receptor class B type I. However, the effect of PDZK1 genetic variants on lipids and metabolic syndrome (MetS) traits remains unknown. This study evaluated the association of 3 PDZK1 single nucleotide polymorphisms (SNP) (i33968C > T, i15371G > A, and i19738C > T) with lipids and risk of MetS and their potential interactions with diet. PDZK1 SNP were genotyped in 1000 participants (481 men, 519 women) included in the Genetics of Lipid Lowering Drugs and Diet Network study. Lipoprotein subfractions were measured by proton NMR spectroscopy and dietary intake was estimated using a validated questionnaire. The PDZK1_i33968C > T polymorphism was associated with MetS (P = 0.034), mainly driven by the association of the minor T allele with higher plasma triglycerides (P = 0.004) and VLDL (P = 0.021), and lower adiponectin concentrations (P = 0.022) than in participants homozygous for the major allele (C). We found a significant gene x BMI x diet interaction, in which the deleterious association of the i33968T allele with MetS was observed in obese participants with high PUFA and carbohydrate (P-values ranging from 0.004 to 0.020) intakes. Conversely, a there was a protective effect in nonobese participants with high PUFA intake (P < 0.05). These findings suggest that PDZK1_i33968C > T genetic variants may be associated with a higher risk of exhibiting MetS. This gene x BMI x diet interaction offers the potential to identify dietary and other lifestyle changes that may obviate the onset of MetS in individuals with a specific genetic background.

SUBMITTER: Junyent M

PROVIDER: S-EPMC2714388 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

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Genetic variants at the PDZ-interacting domain of the scavenger receptor class B type I interact with diet to influence the risk of metabolic syndrome in obese men and women.

Junyent Mireia M Arnett Donna K DK Tsai Michael Y MY Kabagambe Edmond K EK Straka Robert J RJ Province Michael M An Ping P Lai Chao-Qiang CQ Parnell Laurence D LD Shen Jian J Lee Yu-Chi YC Borecki Ingrid I Ordovás Jose M JM

The Journal of nutrition 20090325 5

The scaffolding protein PDZ domain containing 1 (PDZK1) regulates the HDL receptor scavenger receptor class B type I. However, the effect of PDZK1 genetic variants on lipids and metabolic syndrome (MetS) traits remains unknown. This study evaluated the association of 3 PDZK1 single nucleotide polymorphisms (SNP) (i33968C > T, i15371G > A, and i19738C > T) with lipids and risk of MetS and their potential interactions with diet. PDZK1 SNP were genotyped in 1000 participants (481 men, 519 women) in ...[more]

PMID: 19321583

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Project description:Abstract Objectives There is substantial controversy regarding the role of saturated (SFA) and unsaturated fat intake for optimal cardiometabolic health due to the heterogeneity of blood lipid changes in clinical trials. This variance may be due to genetic differences. Studying physiologically relevant variants can elucidate the mechanisms between genotype and metabolism. The objective of this study was to determine relationships between genetic variation, fat intake, and blood lipid concentrations. Methods DNA, blood lipid concentrations (total cholesterol, high-density lipoprotein cholesterol [HDL], and triglycerides [TG]), and 7-day diet records were obtained from 87 adults (25–45 years) with overweight or obesity. Resting energy expenditure (REE) was measured using indirect calorimetry and used to determine implausible intake using a modified Goldberg method (kilocalories/REE). Genetic variants included 22 single nucleotide polymorphisms (SNPs) from genes in lipid metabolism pathways. Variants were analyzed with dietary fat intake (total fat, SFA, monounsaturated fat [MUFA], and polyunsaturated fat) via regression analyses. Results Nine SNPs (ANGPTL3 rs10889337, ANGPTL4 rs7255436, APOE rs1044250, CETP rs5882, FADS1 rs174548 and rs174550, LPL rs13702 and rs328, PPARG rs12639162) were associated with one or more blood lipid traits. Two significant diet-gene interactions were detected: the interaction of total fat intake and LPL rs13702 was associated with HDL concentrations (P = 0.01), and the interaction of MUFA intake and CETP rs5882 was associated with TG concentrations (P = 0.01). Carriers of the minor allele that reported higher total fat intake exhibited higher HDL concentrations, while minor allele carriers with higher MUFA intake exhibited lower TG concentrations. Conclusions Interactions between diet and genes in lipid metabolism pathways were predictors of blood lipid concentrations in adults. Fat intake may not affect blood lipid concentrations uniformly across all individuals. Therefore, personalized diet recommendations for chronic disease prevention are warranted. Funding Sources Support is provided by the Hass Avocado Board, the Division of Nutritional Sciences at the University of Illinois at Urbana-Champaign, the USDA National Institute of Food and Agriculture Hatch Project, and the Agriculture and Food Research Initiative. Supporting Tables, Images and/or Graphs

Dataset Information

Genetic variants at the PDZ-interacting domain of the scavenger receptor class B type I interact with diet to influence the risk of metabolic syndrome in obese men and women.

Publications

Genetic variants at the PDZ-interacting domain of the scavenger receptor class B type I interact with diet to influence the risk of metabolic syndrome in obese men and women.

Similar Datasets

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