Assessment of Interleukin-1 Gene Cluster Polymorphisms in Lone Atrial Fibrillation: New Insight into the Role of Inflammation in Atrial Fibrillation

Authors


Address for reprints: Kazım Serhan Özcan, M.D., Barbaros Mahallesi, Bekir Sıtkı Sezgin Sokak, Özlem Sitesi B blok, Daire:9, 34662, Üsküdar, Istanbul, Turkey. Fax: 90 216 3379719; e-mails: serhandr@gmail.com, serhan_oz@yahoo.com.

Abstract

Background

Systemic inflammation is accepted as one of the pathophysiological mechanisms of atrial fibrillation (AF). The role of inflammation has been shown previously. Interleukin (IL) system is the main modulator of the inflammatory responses and genetic polymorphisms of IL-1 cluster genes are associated with increased risk for inflammatory diseases.

Objectives

To investigate the association between polymorphisms of IL-1 cluster genes and lone AF.

Subjects and Methods

DNA samples were collected from 70 proven lone AF patients and 70 healthy subjects. Genomic DNA was typed for the variable number of the tandem repeat (VNTR) IL-1 receptor antagonist (RN) gene polymorphism, IL-1B –511 C > T(rs16944) promoter polymorphism, and +3953 C > T(rs1143634) polymorphism in exon 5 by polymerase chain reaction.

Results

In lone AF group the frequency of IL-1RN2/2 and IL-1RN1/2 genotypes were higher than in the control group (7.2% vs 4.3% and 48.5% vs 22.8%, respectively; χ2 = 14.1; P = 0.028). The frequency of allele 2 was significantly higher in the lone AF group (32.1% vs 15.7%; χ2 = 10.7; P = 0.005). Allele and genotype distribution of IL-1B –511 C > T and +3953 C > T polymorphisms were not statistically different between the groups. C-reactive protein (CRP) levels were higher in lone AF patients compared to the control group (median = 1.25, interquartile range [IQR] = 0.85 vs median = 1.08, IQR 0.46 mg/L, respectively; P = 0.02). In multivariate regression analysis, presence of allele 2 of IL-1 VNTR polymorphism and elevated plasma high-sensitive-CRP levels were the independent predictors of lone AF.

Conclusion

Presence of allele 2 of VNTR polymorphism of IL-1RN gene may cause increased risk for lone AF probably due to the inadequate limitation of inflammatory reactions.

Ancillary