Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID: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. 1932 83

Uric acid (UA) is the final catabolic product of purine metabolism and elevated levels are associated with diabetes and cardiovascular disease. A recent meta-analysis of genome-wide association studies totalling 28,141 participants identified five novel loci associated with serum UA levels. In our population-based cohort of 7795 subjects, we replicated four of these five loci; PDZK1 (rs12129861, P = 1.07 x 10(-3)), glucokinase regulator protein (GCKR) (rs780094, P = 4.83 x 10(-4)), SLC16A9 (rs742132, P = 0.047) and SLC22A11 (rs17300741, P = 6.13 x 10(-3)), but not LRRC16A (rs742132, P = 0.645). Serum UA concentration is a complex trait, closely associated to renal UA handling (fractional UA excretion, P < 1 x 10(-300)), renal function (serum creatinine, P < 1 x 10(-300)) and the metabolic syndrome (including fasting insulin, P = 2.48 x 10(-232); insulin resistance, P = 2.51 x 10(-258); waist circumference, P < 1 x 10(-300)) and systolic blood pressure (P = 1.93 x 10(-219)). Together these factors explain 67% of the variance in UA levels. Therefore, we sought to determine the potential contribution of these factors to the association of these novel loci with UA levels, by including them as additional explanatory variables in our analyses, and by considering them as alternative response variables. The association with the GCKR locus is attenuated by serum triglycerides and fractional UA excretion. We also observed the GCKR locus to be associated with total cholesterol (P = 7.52 x 10(-6)), triglycerides (P = 2.65 x 10(-9)), fasting glucose (P = 0.011), fractional UA excretion (P = 3.36 x 10(-5)) and high-sensitive CRP (P = 1.18 x 10(-3)) also after adjusting for serum UA levels. We argue that GCKR locus affects serum UA levels through a factor that also affects triglycerides.
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PMID:Replication of the five novel loci for uric acid concentrations and potential mediating mechanisms. 1986 89

The syntrophins alpha (SNTA) and beta 2 (SNTB2) are molecular adaptor proteins shown to stabilize ABCA1, an essential regulator of HDL cholesterol. Furthermore, SNTB2 is involved in glucose stimulated insulin release. Hyperglycemia and dyslipidemia are characteristic features of the metabolic syndrome, a serious public health problem with rising prevalence. Therefore, it is important to understand the role of the syntrophins herein. Mice deficient for both syntrophins (SNTA/B2-/-) have normal insulin and glucose tolerance, hepatic ABCA1 protein and cholesterol. When challenged with a HFD, wild type and SNTA/B2-/- mice have similar weight gain, adiposity, serum and liver triglycerides. Hepatic ABCA1, serum insulin and insulin sensitivity are normal while glucose tolerance is impaired. Liver cholesterol is reduced, and expression of SREBP2 and HMG-CoA-R is increased in the knockout mice. Scavenger receptor-BI (SR-BI) protein is strongly diminished in the liver of SNTA/B2-/- mice while SR-BI binding protein NHERF1 is not changed and PDZK1 is even induced. Knock-down of SNTA, SNTB2 or both has no effect on hepatocyte SR-BI and PDZK1 proteins. Further, SR-BI levels are not reduced in brown adipose tissue of SNTA/B2-/- mice excluding that syntrophins directly stabilize SR-BI. SR-BI stability is regulated by MAPK and phosphorylated ERK2 is induced in the liver of the knock-out mice. Blockage of ERK activity upregulates hepatocyte SR-BI showing that increased MAPK activity contributes to low SR-BI. Sphingomyelin which is well described to regulate cholesterol metabolism is reduced in the liver and serum of the knock-out mice while the size of serum lipoproteins is not affected. Current data exclude a major function of these syntrophins in ABCA1 activity and insulin release but suggest a role in regulating glucose uptake, ERK and SR-BI levels, and sphingomyelin metabolism in obesity.
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PMID:Lipid abnormalities in alpha/beta2-syntrophin null mice are independent from ABCA1. 2562 30