Assessment of Interleukin-1 Gene Cluster Polymorphisms in Lone Atrial Fibrillation: New Insight into the Role of Inflammation in Atrial Fibrillation
Assessment of Interleukin-1 Gene Cluster Polymorphisms in Lone Atrial Fibrillation: New Insight into the Role of Inflammation in Atrial Fibrillation
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DOI：
10.1111/pace.12182
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发表时间：
2013-10-01
影响因子：
1.8
通讯作者：
Bolca, Osman
中科院分区：
文献类型：
--
作者：
Gungor, Baris;Ekmekci, Ahmet;Bolca, Osman
背景：全身性炎症被认为是心房颤动（AF）的病理生理机制之一。炎症的作用之前已经被证明过。白细胞介素（IL）系统是炎症反应的主要调节剂，IL-1簇基因的遗传多态性与炎症性疾病的风险增加有关。目的探讨IL-1基因簇多态性与单纯性房颤的关系。研究对象和方法采集70例单纯性房颤患者和70例健康人群的dna样本。采用聚合酶链反应对基因组DNA进行5外显子串联重复序列（VNTR） IL-1受体拮抗剂（RN）基因多态性、IL-1B - 511c > T（rs16944）启动子多态性和+ 3953c > T（rs1143634）多态性的分型。结果单独AF组患者IL-1RN2/2和IL-1RN2/2基因型频率高于对照组（分别为7.2%比4.3%和48.5%比22.8%）；P = 0.028)。等位基因2的频率在单独房颤组中显著升高(32.1% vs 15.7%; (2) = 10.7；P = 0.005)。IL-1B - 511c > T和+ 3953c > T多态性的等位基因和基因型分布在组间无统计学差异。单独房颤患者的c反应蛋白（CRP）水平高于对照组（中位数= 1.25，四分位数范围[IQR] = 0.85 vs中位数= 1.08,IQR = 0.46 mg/L, P = 0.02）。多因素回归分析显示，IL-1 VNTR多态性等位基因2的存在和血浆高敏crp水平升高是单发房颤的独立预测因素。结论IL-1RN基因VNTR多态性等位基因2的存在可能导致单发房颤的风险增加，可能与炎症反应限制不足有关。
BackgroundSystemic 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.ObjectivesTo investigate the association between polymorphisms of IL-1 cluster genes and lone AF.Subjects and MethodsDNA 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.ResultsIn 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; (2) = 14.1; P = 0.028). The frequency of allele 2 was significantly higher in the lone AF group (32.1% vs 15.7%; (2) = 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.ConclusionPresence 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.