Evidence for an association between the Leu162Val polymorphism of the PPARα gene and decreased fasting serum triglyceride levels in glucose tolerant subjects

Pharmacogenetics

Volumn 13, Issue 7, 2003, Pages 417-423

  Nielsen, Eva Maria Damsgaard ^a   Hansen, Lars ^a,b   Echwald, Søren M ^a   Drivsholm, Thomas ^c   Borch Johnsen, Knut ^a   Ekstrøm, Claus T ^a,d   Hansen, Torben ^a   Pedersen, Oluf ^a,e  

^a STENO DIABETES CENTER   (Denmark)

^b NOVO NORDISK A S   (Denmark)

^c GLOSTRUP UNIVERSITY HOSPITAL   (Denmark)

^d UNIVERSITY OF COPENHAGEN   (Denmark)

^e AARHUS UNIVERSITY   (Denmark)

Author keywords

Genetic epidemiology; Leu162Val; Mutation analysis; Normal glucose tolerance; Polymorphisms; PPAR ; Serum triglyceride; Type 2 diabetes

Indexed keywords

ALANINE; ARGININE; CELL NUCLEUS RECEPTOR; GLYCINE; HORMONE RECEPTOR; LEUCINE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; TRANSCRIPTION FACTOR; TRIACYLGLYCEROL; VALINE; CELL RECEPTOR; INSULIN;

ADULT; AGED; ALLELE; ARTICLE; BLOOD SAMPLING; DIET RESTRICTION; EXON; FATTY ACID OXIDATION; FEMALE; GENE LOCATION; GENE MUTATION; GENETIC ASSOCIATION; GENETIC POLYMORPHISM; GENETIC VARIABILITY; GLUCOSE BLOOD LEVEL; GLUCOSE TOLERANCE; HUMAN; LIPID METABOLISM; MAJOR CLINICAL STUDY; MALE; NON INSULIN DEPENDENT DIABETES MELLITUS; PRIORITY JOURNAL; TRIACYLGLYCEROL BLOOD LEVEL; BLOOD; BODY CONSTITUTION; CASE CONTROL STUDY; CAUCASIAN; COMPARATIVE STUDY; DENMARK; GENE FREQUENCY; GENETICS; GLUCOSE TOLERANCE TEST; HETEROZYGOTE; METABOLISM; MIDDLE AGED; NUCLEOTIDE SEQUENCE; POINT MUTATION;

ADULT; AGED; ALLELES; BLOOD GLUCOSE; BODY CONSTITUTION; CASE-CONTROL STUDIES; DENMARK; DIABETES MELLITUS, TYPE 2; DNA MUTATIONAL ANALYSIS; EUROPEAN CONTINENTAL ANCESTRY GROUP; FASTING; FEMALE; GENE FREQUENCY; GLUCOSE TOLERANCE TEST; HETEROZYGOTE; HUMANS; INSULIN; MALE; MIDDLE AGED; POINT MUTATION; POLYMORPHISM, GENETIC; RECEPTORS, CYTOPLASMIC AND NUCLEAR; TRANSCRIPTION FACTORS; TRIGLYCERIDES; VALINE; VARIATION (GENETICS);

EID: 0041866347     PISSN: 0960314X     EISSN: None     Source Type: Journal    
DOI: 10.1097/00008571-200307000-00007     Document Type: Article

References (31)

1. Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, Schtz G, Umesono K, et al. The nuclear receptor superfamily: the second decade. Cell 1995; 83:835-839.
2. Desvergne B, Wahli W, Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr Rev 1999; 20:649-688.
3. DeFronzo RA. Insulin resistance: a multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidaemia and atherosclerosis. Neth J Med 1997; 50:191-197.
4. Sher T, Yi HF, McBride OW, Gonzalez FJ. cDNA cloning, chromosomal mapping, and functional characterization of the human peroxisome proliferator activated receptor. Biochemistry 1993; 32:5598-5604.
5. Auboeuf D, Rieusset J, Fajas L, Vallier P, Frering V, Riou JP, et al. Tissue distribution and quantification of the expression of mRNAs of peroxisome proliferator-activated receptors and liver X receptor-alpha in humans: no alteration in adipose tissue of obese and NIDDM patients. Diabetes 1997; 46:1319-1327.
6. Braissant O, Foufelle F, Scotto C, Dauca M, Wahli W. Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat. Endocrinology 1996; 137:354-366.
7. Schoonjans K, Peinado-Onsurbe J, Lefebvre AM, Heyman RA, Briggs M, Deeb S, et al. PPARalpha and PPARgamma activators direct a distinct tissue-specific transcriptional response via a PPRE in the lipoprotein lipase gene. EMBO J 1996; 15:5336-5348.
8. Hertz R, Bishara-Shieban J, Bar-Tana J. Mode of action of peroxisome proliferators as hypolipidemic drugs. Suppression of apolipoprotein C-III. J Biol Chem 1995; 270:13470-13475.
9. Staels B, Dallongeville J, Auwerx J, Schoonjans K, Leitersdorf E, Fruchart JC, Mechanism of action of fibrates on lipid and lipoprotein metabolism. Circulation 1998; 98:2088-2093.
10. Gervois P, Chopin-Delannoy S, Fadel A, Dubois G, Kosykh V, Fruchart JC, et al. Fibrates increase human REV-ERBalpha expression in liver via a novel peroxisome proliferator-activated receptor response element. Mol Endocrinol 1999; 13:400-409.
11. Juge-Aubry C, Pernin A, Favez T, Burger AG, Wahli W, Meier CA, et al. DNA binding properties of peroxisome proliferator-activated receptor subtypes on various natural peroxisome proliferator response elements. Importance of the 5′-flanking region. J Biol Chem 1997; 272: 25252-25259.
12. Palmer CNA, Hsu MH, Griffin KJ, Johnson EF. Novel sequence determinants in peroxisome proliferator signaling. J Biol Chem 1995; 270: 16114-16121.
13. Lewitt MS, Brismar K, Wang J, Wivall-Helleryd IL, Sindelar P, Gonzalez FJ, et al. Responses of insulin-like growth factor (IGF)-I and IGF-binding proteins to nutritional status in peroxisome proliferator-activated receptor-alpha knockout mice. Growth Horm IGF Res 2001; 11:303-313.
14. Gonzalez FJ. Recent update on the PPAR alpha-null mouse. Biochimie 1997; 79:139-144.
15. Peters JM, Hennuyer N, Staels B, Fruchart JC, Fievet C, Gonzalez FJ, et al. Alterations in lipoprotein metabolism in peroxisome proliferator-activated receptor alpha-deficient mice. J Biol Chem 1997; 272: 27307-27312.
16. Lee SS, Pineau T, Drago J, Lee EJ, Owens JW, Kroetz DL, et al. Targeted disruption of the alpha isoform of the peroxisome proliferator-activated receptor gene in mice results in abolishment of the pleiotropic effects of peroxisome proliferators. Mol Cell Biol 1995; 15:3012-3022.
17. Evans D, Aberle J, Wendt D, Wolf A, Beisiegel U, Mann WA. A polymorphism, L162V, in the peroxisome proliferator-activated receptor α (PPARα) gene is associated with lower body mass index in patients with non-insulin-dependent diabetes mellitus. J Mol Med 2001; 79:198-204.
18. Puckey LH, Knight BL. Variation at position 162 of peroxisome proliferator-activated receptor α does not influence the effect of fibrates on cholesterol or triacylglycerol concentrations in hyperlipidaemic subjects. Pharmacogenetics 2001; 11:619-624.
19. Flavell DM, Torra IP, Jamshidi Y, Evans D, Diamond JR, Elkeles RS, et al. Variation in the PPAR alpha gene is associated with altered function in vitro and plasma lipid concentrations in type II diabetic subjects. Diabetologia 2000; 43:673-680.
20. Lacquemant C, Lepretre F, Torra IP, Manraj M, Charpentier G, Ruiz J, et al. Mutation screening of the PPAR alpha gene in type 2 diabetes associated with coronary heart disease. Diabetes Metab 2000; 26: 393-401.
21. Sapone A, Peters JM, Sakai S, Tomita S, Papiha SS, Dai RK, et al. The human peroxisome proliferator-activated receptor α gene: identification and functional characterization of two natural allelic variants. Pharmacogenetics 2000; 10:321-333.
22. Vehl MC, Lepage P, Gaudet D, Brewer CG, Betard C, Perren P, et al. Molecular scanning of the human PPAR alpha gene: association of the L162V mutation with hyperapobetalipoproteinemia. J Lipid Res 2000; 41:945-952.
23. Drivsholm T, Ibsen H, Schroll M, Davidsen M, Borch-Johnsen K. Increasing prevalence of diabetes mellitus and impaired glucose tolerance among 60-year-old Danes. Diabet Med 2001; 18:126-132.
24. Clausen JO, Borch-Johnsen K, Ibsen H, Bergman RN, Hougaard P, Winther K, et al. Insulin sensitivity index, acute insulin response, and glucose effectiveness in a population-based sample of 380 young healthy Caucasians. Analysis of the impact of gender, body fat, physical fitness, and life-style factors. J Clin Invest 1996; 98:1195-1209.
25. World Health Organization. Definition, Diagnosis and Classification of Diabetes Mellitus and Its Complications. Part 1: Diagnosis and Classification of Diabetes Mellitus. Geneva: Department of Noncommunicable Disease Surveillance; 1999.
26. Hansen T, Andersen CB, Echwald SM, Urhammer SA, Clausen JO, Vestergaard H, et al. Identification of a common amino acid polymorphism in the p85alpha regulatory subunit of phosphatidylinositol 3-kinase: effects on glucose disappearance constant, glucose effectiveness, and the insulin sensitivity index. Diabetes 1997; 46:494-501.
27. Costet P, Legendre C, More J, Edgar A, Galtier P, Pineau T. Peroxisome proliferator-activated receptor alpha-isoform deficiency leads to progressive dyslipidemia with sexually dimorphic obesity and steatosis. J Biol Chem 1998; 273:29577-29585.
28. Fleiss JL. The statistical basis of meta-analysis. Stat Meth Med Res 1993; 2:121-145.
29. Brisson D, Ledoux K, Bosse Y, St Pierre J, Julien P, Perron P, et al. Effect of apolipoprotein E, peroxisome proliferator-activated receptor alpha and lipoprotein lipase gene mutations on the ability of fenofibrate to improve lipid profiles and reach clinical guideline targets among hypertriglyceridemic patients. Pharmacogenetics 2002; 12:313-320.
30. 227Ala polymorphism in the peroxisome proliferator activated receptor alpha (PPAR alpha) gene is associated with variations in serum lipid levels. J Med Genet 2002; 39:189-191.
31. Myers KA, Lambe KG, Aldridge TC, Macdonald N, Tugwood JD. Amino acid residues in both the DNA-binding and ligand-binding domains influence transcriptional activity of the human peroxisome proliferator-activated receptor alpha. Biochem Biophys Res Commun 1997; 239:522-526.