title: Genetic variation within the APPL locus is not associated with metabolic or inflammatory traits in a healthy White population.
abstract: OBJECTIVE
  APPL1 (adaptor protein containing PH domain, PTB domain and leucine zipper motif 1) is the first identified cytosolic protein that directly binds to adiponectin receptors and mediates cellular responses to adiponectin. We set out to determine whether genetic variation within the APPL locus (encoding APPL1) contributes to insulin resistance, changes in lipid metabolism or inflammatory parameters in a healthy White population.
  
  
  METHODS
  We genotyped 640 healthy subjects with and without a family history of diabetes for the four single nucleotide polymorphisms (SNPs) rs6774584, rs3087684, rs17791685 and rs528035 and performed correlational analyses with metabolic and inflammatory traits.
  
  
  RESULTS
  SNPs rs6774584, rs3087684, rs17791685 and rs528035 are representative of the four blocks of high linkage disequilibrium covering a 78-kb genomic locus that harbours the APPL gene. None of these SNPs correlated with anthropometric data (gender, age, body mass index, body fat, waist-hip ratio) or with family history of diabetes. Furthermore, no correlations were found with parameters of insulin sensitivity or insulin secretion. None of the SNPs was correlated with ectopic lipid content or with plasma lipids (non-esterified fatty acids, glycerol, triglycerides, total cholesterol, high-density lipoprotein-, low-density lipoprotein-cholesterol). Moreover, no correlations were detected with leucocyte measures or plasma concentrations of C-reactive protein, monocyte chemoattractant protein 1, interleukin 6 or tumour necrosis factor-alpha. Finally, diplotypes derived from these SNPs did not reveal correlations with insulin sensitivity, insulin secretion, lipid measures or inflammatory parameters either.
  
  
  CONCLUSIONS
  We conclude that genetic variation within the APPL locus may not play a major role in the development of prediabetes phenotypes.
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Eberhard-Karls-University Tübingen, Tübingen, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Staiger
authors.forename: F
authors.initials: F
authors.lastname: Machicao
authors.forename: J
authors.initials: J
authors.lastname: Machann
authors.forename: F
authors.initials: F
authors.lastname: Schick
authors.forename: T
authors.initials: T
authors.lastname: Kuulasmaa
authors.forename: M
authors.initials: M
authors.lastname: Laakso
authors.forename: A
authors.initials: A
authors.lastname: Fritsche
authors.forename: N
authors.initials: N
authors.lastname: Stefan
authors.forename: H-U
authors.initials: HU
authors.lastname: Häring
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D052242:Adiponectin / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D050171:Dyslipidemias / Q000378:metabolism; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D007249:Inflammation; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D050356:Lipid Metabolism / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011236:Prediabetic State / Q000235:genetics*; D012307:Risk Factors
chemical_list: C464801:APPL1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D052242:Adiponectin; D002352:Carrier Proteins