title: Common variants in the periostin gene influence development of atherosclerosis in young persons.
abstract: OBJECTIVE
  We investigated the influence of genetic variants (rare and common) in the gene encoding periostin (POSTN) on atherosclerosis as measured in arterial specimens from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study.
  
  
  RESULTS
  A comprehensive survey of common POSTN variants (87 single-nucleotide polymorphisms [SNPs]) in PDAY subjects (n = 2527) identified numerous SNPs associated with raised lesions in abdominal aorta and with fatty streaks in thoracic aorta. These SNPs belonged to a small number of correlation bins that spanned the entire locus. To examine effects of rare variants, we resequenced POSTN functional regions in PDAY cases with raised lesions (n = 291) and controls with no raised lesions (n = 294). However, we found no significant associations with case-control status for carriers of POSTN rare variants using the weighted-sum method for rare variant analysis.
  
  
  CONCLUSIONS
  We identified common variants in POSTN that are associated with arterial lesions in young persons from the PDAY study. This finding strongly supports a role for periostin in atherogenesis, as suggested by recent proteomics analysis that found abundant expression of periostin in atherosclerotic lesions. Genetic variation may influence atherosclerosis via periostin's known involvement in multiple relevant pathways, including angiogenesis, vascular remodeling, and stimulation of migration and differentiation of vascular smooth muscle cells.
authors.affiliation: Human Genetics Center, University of Texas Health Science Center at Houston, TX, USA. james.e.hixson@uth.tmc.edu
authors.forename: James E
authors.initials: JE
authors.lastname: Hixson
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Shimmin
authors.forename: May E
authors.initials: ME
authors.lastname: Montasser
authors.forename: Do-Kyun
authors.initials: DK
authors.lastname: Kim
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhong
authors.forename: Heladio
authors.initials: H
authors.lastname: Ibarguen
authors.forename: Jack
authors.initials: J
authors.lastname: Follis
authors.forename: Gray
authors.initials: G
authors.lastname: Malcom
authors.forename: Jack
authors.initials: J
authors.lastname: Strong
authors.forename: Tim
authors.initials: T
authors.lastname: Howard
authors.forename: Carl
authors.initials: C
authors.lastname: Langefeld
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Liu
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.forename: Craig
authors.initials: C
authors.lastname: Johnson
authors.forename: David
authors.initials: D
authors.lastname: Herrington
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001012:Aorta, Abdominal / Q000473:pathology; D001013:Aorta, Thoracic / Q000473:pathology; D001018:Aortic Diseases / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D050197:Atherosclerosis / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D001344:Autopsy; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D016014:Linear Models; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012307:Risk Factors; D014481:United States; D055815:Young Adult
chemical_list: D015815:Cell Adhesion Molecules; C512835:POSTN protein, human