title: Search for Genetic Variant in the Apelin Gene by Resequencing and Association Study in European Subjects.
abstract: OBJECTIVE
  Apelin is a peptide produced and secreted by white adipose tissue. It is synthesized as preproapelin, a protein containing 77 aminoacids which is then cleaved to shorter active fragments. As an adipokine, apelin plays a role in the regulation of many biological functions, including body energy homeostasis and glucose metabolism, water balance, and immunity. We have recently demonstrated that subjects with type 2 diabetes (T2D) have significantly higher serum apelin levels compared with controls, and that these levels associate with fasting glucose, basal disposition index, age, and diagnosis of T2D. The first aim of this study was to search for sequence variants in the apelin gene (APLN), located on chromosome Xq25-q26.1 that may associate with serum levels of apelin. The second aim was to analyze the possible association between diabetes and diabetes-related traits and APLN variants.
  
  
  METHODS
  We designed a two-step genetic association study. Step one consisted of an initial screen of 100 individuals selected from the extremes of the apelin distribution levels wherein we sequenced the APLN gene to identify common variants. In step two, the rs181301686 with a minor allele frequency >0.2 was genotyped in 917 individuals to explore its association with T2D and diabetes-related traits.
  
  
  RESULTS
  Five sequence variations were found across the APLN gene. To test for association with apelin levels, the rs181301686 and rs2281069 single-nucleotide polymorphisms were genotyped in 256 subjects for whom serum apelin levels were available. No significant differences were observed in apelin levels between genotypes. Association analysis in 917 individuals did not show significant differences between APLN genotypes and diabetes and diabetes-related traits.
  
  
  CONCLUSIONS
  Resequencing of the apelin gene in subjects stratified by low or high apelin levels identified five APLN variants in an European population. No association was found between the most frequent variant, diabetes, and metabolic parameters.
authors.affiliation: 1 Department of Experimental Medicine, Sapienza University of Rome , Rome, Italy .
authors.forename: Federica
authors.initials: F
authors.lastname: Sentinelli
authors.affiliation: 1 Department of Experimental Medicine, Sapienza University of Rome , Rome, Italy .
authors.forename: Danila
authors.initials: D
authors.lastname: Capoccia
authors.affiliation: 1 Department of Experimental Medicine, Sapienza University of Rome , Rome, Italy .
authors.forename: Laura
authors.initials: L
authors.lastname: Bertoccini
authors.affiliation: 2 Internal Medicine Unit, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome , Rome, Italy .
authors.forename: Ilaria
authors.initials: I
authors.lastname: Barchetta
authors.affiliation: 3 Endocrinology and Diabetes, Department of Medical Sciences, University of Cagliari , Cagliari, Italy .
authors.forename: Michela
authors.initials: M
authors.lastname: Incani
authors.affiliation: 1 Department of Experimental Medicine, Sapienza University of Rome , Rome, Italy .
authors.forename: Federica
authors.initials: F
authors.lastname: Coccia
authors.affiliation: 3 Endocrinology and Diabetes, Department of Medical Sciences, University of Cagliari , Cagliari, Italy .
authors.forename: Ettore
authors.initials: E
authors.lastname: Manconi
authors.affiliation: 1 Department of Experimental Medicine, Sapienza University of Rome , Rome, Italy .
authors.forename: Andrea
authors.initials: A
authors.lastname: Lenzi
authors.affiliation: 3 Endocrinology and Diabetes, Department of Medical Sciences, University of Cagliari , Cagliari, Italy .
authors.forename: Efisio
authors.initials: E
authors.lastname: Cossu
authors.affiliation: 1 Department of Experimental Medicine, Sapienza University of Rome , Rome, Italy .
authors.forename: Frida
authors.initials: F
authors.lastname: Leonetti
authors.affiliation: 2 Internal Medicine Unit, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome , Rome, Italy .
authors.forename: Maria Gisella
authors.initials: MG
authors.lastname: Cavallo
authors.affiliation: 1 Department of Experimental Medicine, Sapienza University of Rome , Rome, Italy .|3 Endocrinology and Diabetes, Department of Medical Sciences, University of Cagliari , Cagliari, Italy .
authors.forename: Marco Giorgio
authors.initials: MG
authors.lastname: Baroni
mesh_terms: D000328:Adult; D000073861:Apelin; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood / Q000235:genetics*; D007558:Italy; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: C115436:APLN protein, human; D000073861:Apelin; D036341:Intercellular Signaling Peptides and Proteins