title: Analysis of the association between an insertion/deletion polymorphism within the 3' untranslated region of COL1A2 and chronic venous insufficiency.
abstract: BACKGROUND
  Chronic venous insufficiency (CVI) is a common cause of leg pain and swelling and is commonly associated with varicose veins. It has significant socioeconomic consequences and is among the most common problems encountered in surgical practice. Although our current understanding of the pathogenesis of CVI is far from clear, there is a growing body of evidence suggesting a genetic contribution to the etiology of CVI.
  
  
  METHODS
  By analyzing 254 CVI cases and 508 healthy controls in a Chinese population, we used a candidate gene approach to evaluate the association between a 7-base pair insertion/deletion (indel) polymorphism (rs3917) in the 3' untranslated region (3'UTR) of the alpha-2 type I collagen gene (COL1A2) and CVI susceptibility. Logistic regression was used to analyze the association between rs3917 and CVI risk, adjusted for sex and age. Computational modeling was used to predict potential molecular mechanisms underlying the association.
  
  
  RESULTS
  Logistic regression analysis revealed that subjects carrying indel or deletion/deletion genotypes had a significantly increased risk for CVI than individuals carrying insertion/insertion genotypes (adjusted odds ratio, 1.64; 95% confidence interval [CI], 1.10-2.45; P = 0.010). Carrying the 7-base pair deletion allele was associated with a 1.60-fold risk for CVI (95% CI, 1.11-2.31; P = 0.008). Computational modeling suggests that the rs3917 insertion allele lies within a predicted binding site (seed region) for microRNA-382 and that the deletion allele alters the affinity of microRNA-mRNA binding by disrupting the local structure of COL1A2 mRNA, presumably allowing for upregulated COL1A2 expression.
  
  
  CONCLUSIONS
  Taken together, our data suggest that common genetic variations in COL1A2 may influence CVI risk, possibly through microRNA-382-mediated regulation. Replication of our studies in other populations will strengthen our understanding of this association.
authors.affiliation: Department of Vascular Surgery, Suzhou Municipal Hospital, Affiliated Suzhou Hospital of Nanjing Medical University, Jiangsu, China.
authors.forename: Yiqi
authors.initials: Y
authors.lastname: Jin
authors.forename: Guoxiong
authors.initials: G
authors.lastname: Xu
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
authors.forename: Dayong
authors.initials: D
authors.lastname: Zhou
authors.forename: Xianchen
authors.initials: X
authors.lastname: Huang
authors.forename: Liming
authors.initials: L
authors.lastname: Shen
mesh_terms: D020413:3' Untranslated Regions; D000368:Aged; D001665:Binding Sites; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002681:China; D002908:Chronic Disease; D024042:Collagen Type I / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D054643:INDEL Mutation; D016015:Logistic Models; D008297:Male; D035683:MicroRNAs / Q000378:metabolism; D008875:Middle Aged; D062105:Molecular Docking Simulation; D009690:Nucleic Acid Conformation; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic; D011379:Prognosis; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism; D012307:Risk Factors; D014689:Venous Insufficiency / Q000175:diagnosis / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D024042:Collagen Type I; C555413:MIRN382 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger