title: Mutation analysis of the human adipocyte-specific apM-1 gene.
abstract: BACKGROUND
  The aim of this study was to analyse the human adipocyte-specific apM-1 gene for sequence variations.
  
  
  METHODS
  Sequence analysis was performed in 344 randomly chosen blood samples using a capillary sequencer.
  
  
  RESULTS
  Whereas no mutations were detected in intronic regions and in 2.7 kb of the promoter, two sequence variations were found within the coding sequence of apM-1. For both mutations, a polymerase chain reaction-(PCR) based restriction fragment length polymorphism (RFLP) analysis was developed, which provided a rapid screening method. A conservative T --> G transition at nucleotide + 45 within exon-2 [Gly15Gly] was detected with an allelic frequency of 0.9 for the wild-type allele and 0.1 for the mutated allele. In addition, a missense point mutation at nucleotide + 331 within exon-3 [Tyr111His] was detected with an allelic frequency of 0.97 for the wild-type allele and 0.03 for the mutated allele. This mutation replaces a tyrosine by an histidine within the carboxyterminal globular domain of apM-1. Concerning the Gly15Gly polymorphism, the TT genotype was found in 275 subjects (79.9%), the TG genotype in 67 subjects (19.5%) and the GG genotype in 2 subjects (0.6%): one with maturity onset diabetes of young age (MODY-diabetes) and one with Lipoatrophic Diabetes Syndrome (LPDS). Concerning the Tyr111His polymorphism, the TT genotype was found in 328 subjects (95.4%), the TC genotype in 15 subjects (4.3%) and the CC genotype in 1 subject (0.3%).
  
  
  CONCLUSIONS
  The existence of two yet unknown mutations within the apM-1 gene was demonstrated and RFLP analysis was established for rapid screening. Well defined cohorts of patients are necessary to determine the putative role of apM-1 gene mutations in the pathogenesis of metabolic disorders.
authors.affiliation: Department of Internal Medicine I, Institute of Clinical Chemistry, University of Regensburg, Germany. andreas.schaeffler@klinik.uni-regensburg.de
authors.forename: A
authors.initials: A
authors.lastname: Schäffler
authors.forename: N
authors.initials: N
authors.lastname: Barth
authors.forename: K D
authors.initials: KD
authors.lastname: Palitzsch
authors.forename: W
authors.initials: W
authors.lastname: Drobnik
authors.forename: J
authors.initials: J
authors.lastname: Schölmerich
authors.forename: G
authors.initials: G
authors.lastname: Schmitz
mesh_terms: D017667:Adipocytes / Q000737:chemistry / Q000502:physiology; D052242:Adiponectin; D000328:Adult; D015992:Body Mass Index; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D003923:Diabetes Mellitus, Lipoatrophic / Q000235:genetics* / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism; D005091:Exons; D005260:Female; D005787:Gene Frequency; D006720:Homozygote; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008074:Lipoproteins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D012150:Polymorphism, Restriction Fragment Length; D011506:Proteins / Q000235:genetics*
chemical_list: D052242:Adiponectin; D036341:Intercellular Signaling Peptides and Proteins; D008074:Lipoproteins; D011506:Proteins