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A Val227Ala polymorphism in the peroxisome proliferator activated receptor α (PPARα) gene is associated with variations in serum lipid levels
  1. K Yamakawa-Kobayashi1,
  2. H Ishiguro1,
  3. T Arinami1,
  4. R Miyazaki2,
  5. H Hamaguchi1
  1. 1Department of Medical Genetics, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
  2. 2Department of Internal Medicine, Kudanzaka Hospital, Kudan-minami, Tokyo 102-0074, Japan
  1. Correspondence to:
 Dr K Yamakawa-Kobayashi, Department of Medical Genetics Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan;

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Peroxisome proliferator activated receptors (PPARs) are ligand activated transcription factors that belong to the nuclear receptor superfamily.1, 2 PPARs regulate gene transcription by heterodimerising with retinoic X receptors and binding to DNA sequences, termed PPAR response elements (PPRE), in the promoters of target genes.2, 3

Three different PPAR genes (α, δ/β, and γ), each displaying distinct tissue and developmental expression patterns, have been identified.4, 5PPARα, the first member of the PPAR family to be identified, was cloned as an orphan receptor activated by agents that induce peroxisome proliferation.6 It is expressed primarily in tissues with high levels of fatty acid oxidation, such as those in liver, kidney, heart, and muscle.4, 6 Most target genes of PPARα encode enzymes involved in oxidation of cellular fatty acids, lipid transporters, and apolipoproteins.1, 7 Furthermore, PPARα is known to mediate the actions of fibrates, which are hypolipidaemic drugs that decrease plasma triglycerides and increase high density lipoprotein (HDL) cholesterol concentrations.8, 9 Numerous in vivo and in vitro studies have suggested that PPARα is a key metabolic regulator involved in lipid and glucose homeostasis.1, 10–12 Recently, a Leu162Val polymorphism was identified in the PPARα gene, and this polymorphism was shown to influence plasma lipid concentrations, especially in type II diabetes patients.13, 14 In the present study, we have screened for polymorphisms in the PPARα gene to determine whether genomic variations in this gene influence serum lipid levels, glucose levels, and body mass index (BMI) in healthy subjects.


Taking part in this study were 401 unrelated and apparently healthy subjects (207 men and 194 women) who visited medical clinics in Tokyo for routine medical check ups. They were all Japanese. They ranged in age from 29 to 75 years with a mean …

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