白细胞介素6基因-597G／A与-572C／G多态性对心房颤动发病易感性的影响

Effects of interleukin-6 gene -597G/A and -572C/G polymorphisms on susceptibility to atrial fibrillation and its functional study

目的了解白细胞介素6（IL-6）基因-597G／A及-572C／G多态性对心房颤动（房颤）发病易感性的影响。方法应用聚合酶链反应．限制性片段长度多态性（PCR—RFLP）方法，测定291例房颤患者（房颤组）和325例正常对照者（对照组）的IL-6基因．597G／A及-572C／G多态性，探讨其与房颤的相关关系、对不同病因及不同临床类型房颤的影响，观察其对左心房内径（LAD）、血清IL-6水平及外周血单个核细胞（PBMC）产生IL．6能力的影响。结果在研究人群中，-597位点仅发现有GG基因型。-572位点存在3种基因型，房颤组CG＋GG基因型和G等位基因频率分别为51．55％和29．90％，与对照组相比差异有统计学意义（P〈0．001），对照组中分别为35．38％、18．77％；G等位基因携带者患房颤的风险是CC基因型的1．94倍（95％CI：1．41～2．68，P〈0．001）；校正了其他因素的影响后，CG-GG基因型仍然是房颤发生的独立危险因素（OR=1．63，95％CI：1．05～2．51，P〈0．05）。孤立性、高血压、冠心病等不同病因以及不同临床类型房颤间-572C／G多态性分布差异无统计学意义（P〉O．05）。房颤组CG±GG基因型人群LAD值高于CC基因型人群[（37．51±8．78）mm对（35．26±5．52）mm，P〈0．05]。不同基因型人群血清IL-6水平差异无统计学意义（P〉0．05），但对照组G等位基因携带者PBMC随培养时间的延长上清液IL-6含量高于CC基因型人群（P〈0．05）。结论IL-6基因-597G／A多态性可能与中国汉族人群房颤发病易感性无关；而-572C／G多态性可能是该人群房颤发病的易感基因之-，该多态性存在-定的功能。

Objective To observe the effects of interleukin-6 （IL-6）gene polymorphisms on susceptibility to atrial fibrillation （AF） and to analyze the function of IL-6 gene polymorphisms. Methods IL- 6 gene -597G/A and -572C/G polymorphisms were genotyped in 291 AF patients and 325 healthy adults by PCR-RFLP method. The distributions of polymorphisms among AF patients with different etiology and different clinical types were observed.Effects of IL-6 genotypes on left atrial diameter （LAD） , serum IL-6 levels and the ability of IL-6 production from cultured peripheral blood mononuclear cells （PBMC）were studied. Results There wash＇ t IL-6 gene -597G/A polymorphism in two groups.-572CG＋GG genotype and G allele were more frequent in AF patients than that in control group（P〈0. 001 ）.The relative risk for G allele carrier to suffer from AF was 1.94 times of CC genotype individual （95%CI： 1.41-2. 68,P〈0. 001）.After adjusted effects of other factors,-572C/G genotype still was an independent risk factor of AF（ OR= 1.63,95%C1： 1.05- 2. 51 ,P〈0. 05）.However, the distributions of IL-6 gene -572C/G polymorphism were not significantly different among AF patients with lone AF, hypertension and coronary artery diseases,and among patients with paroxysmal,persistent and permanent AF（ P〉0.05 ）.LAD of patients with -572CG＋GG genotype was larger than that of -572CC genotype in AF group （ 37. 51-＋ 8.78） mm vs （ 35. 26＋ 5. 52） mm, t =-2. 5, P〈 0. 05）. There were no statistics differences about serum IL-6 levels between genotypes among two groups （P〉0. 05 ）.After 24 h PBMC culture in basical status or after 12 h and 24 h PBMC culture in oxidized low density lipoprotein stimulated sta- tus, the IL-6 concentrations in superuatant were significantly higher in subjects with CG＋ GG genotype than those with CC genotype（P〈0. 05）. Coneluslon IL-6 gene -597G/A polymorphism was not associated with susceptibility to AF, but -572G allele may be a genetic susceptibility factor to AF attack in Chinese Hans population.This may be related to the function of -572C/G polymorphism, with enlarger LAD and higher expression of IL-6 in-572G cartier.