Analysis of the Association Between an Insertion/Deletion Polymorphism Within the 3′ Untranslated Region of COL1A2 and Chronic Venous Insufficiency

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.