title: Molecular scanning of the human peroxisome proliferator activated receptor gamma (hPPAR gamma) gene in diabetic Caucasians: identification of a Pro12Ala PPAR gamma 2 missense mutation.
abstract: Peroxisome proliferator activated receptor-gamma (PPAR gamma) is a nuclear receptor that regulates adipocyte differentiation, and possibly lipid metabolism and insulin sensitivity. As such, PPAR gamma is a promising candidate gene for several human disorders including obesity and type 2 diabetes mellitus. Screening for mutations in the entire coding region of the PPAR gamma gene (both gamma 1 and gamma 2 isoforms) was performed with DNA of 26 diabetic Caucasians with or without obesity. Two base substitutions were identified: a silent mutation at nucleotide 1431 (CACHis-->CATHis) and a missense mutation (CCGPro-->GCGAla) at codon 12 of PPAR gamma 2. The allele frequency of the Pro12Ala PPAR gamma 2 variant was 0.12 in Caucasian Americans, 0.10 in Mexican Americans, 0.08 in Samoans, 0.03 in African Americans, 0.02 in Nauruans, and 0.01 in Chinese. We conclude that the Pro12Ala PPAR gamma 2 gene variant is present in diverse populations. Further studies of the Pro12Ala variant will determine its relevance to obesity, insulin resistance, and type 2 diabetes.
authors.affiliation: Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Yen
authors.forename: B A
authors.initials: BA
authors.lastname: Beamer
authors.forename: C
authors.initials: C
authors.lastname: Negri
authors.forename: K
authors.initials: K
authors.lastname: Silver
authors.forename: K A
authors.initials: KA
authors.lastname: Brown
authors.forename: D P
authors.initials: DP
authors.lastname: Yarnall
authors.forename: D K
authors.initials: DK
authors.lastname: Burns
authors.forename: J
authors.initials: J
authors.lastname: Roth
authors.forename: A R
authors.initials: AR
authors.lastname: Shuldiner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005091:Exons; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009765:Obesity / Q000235:genetics; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics*; D014481:United States; D044465:White People / Q000235:genetics*
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors