Hernesniemi Jussi A, Karhunen Pekka J, Rontu Riikka, Ilveskoski Erkki, Kajander Olli, Goebeler Sirkka, Viiri Leena E, Pessi Tanja, Hurme Mikko, Lehtimäki Terho
Laboratory of Atherosclerosis Genetics, Tampere University Hospital and Department of Clinical Chemistry, Medical School, University of Tampere, Tampere, Finland.
Atherosclerosis. 2008 Feb;196(2):643-9. doi: 10.1016/j.atherosclerosis.2007.07.018. Epub 2007 Aug 31.
The increased plasma concentrations of pro-atherogenic and cardiomyocyte hypertrophic cytokine interleukin 18 (IL-18) predict mortality in patients with coronary heart disease (CHD) in addition to predicting the outcome of heart failure. The IL-18 gene has a functional -137G/C polymorphism (rs187238) in the promoter region. The C allele carriage is associated with attenuated IL-18 production. The effect of IL-18 genotype on SCD is unknown. We studied the association of the IL-18 gene -137G/C polymorphism with the occurrence of sudden cardiac death (SCD).
Using the TaqMan 5' nuclease assay, we genotyped two independent consecutive and prospective autopsy series which were included in the Helsinki Sudden Death Study.
Of the 663 men, 359 (54.1%) had the wild-type GG-genotype, 261 (39.4%) were heterozygotes (CG) and 43 (6.5%) were CC homozygotes. Compared to the GG homozygotes, the C allele carriers (i.e. subjects having CC or CG genotypes) had a lower adjusted risk for SCD from any cause (odds ratio [OR] 0.49; 95% confidence interval [CI], 0.31-0.77, p=0.002), for SCD due to CHD (OR 0.51; 95% CI, 0.32-0.82, p=0.005), and for SCD caused by non-coronary heart diseases (OR 0.34; 95% CI 0.13-0.90, p=0.030).
IL-18 promoter -137G/C polymorphism, which regulates the expression of IL-18, is an important predictor of SCD from any cause as well as SCD in patients with and without underlying CHD.
促动脉粥样硬化和心肌细胞肥大的细胞因子白细胞介素18（IL-18）的血浆浓度升高，除了可预测心力衰竭的预后外，还能预测冠心病（CHD）患者的死亡率。IL-18基因启动子区域存在功能性-137G/C多态性（rs187238）。携带C等位基因与IL-18产生减少有关。IL-18基因型对心源性猝死（SCD）的影响尚不清楚。我们研究了IL-18基因-137G/C多态性与心源性猝死（SCD）发生之间的关联。
我们使用TaqMan 5'核酸酶分析技术，对两个独立的连续前瞻性尸检系列进行基因分型，这些系列纳入了赫尔辛基猝死研究。
在663名男性中，359名（54.1%）具有野生型GG基因型，261名（39.4%）为杂合子（CG），43名（6.5%）为CC纯合子。与GG纯合子相比，C等位基因携带者（即具有CC或CG基因型的受试者）因任何原因导致的SCD调整后风险较低（优势比[OR]0.49；95%置信区间[CI]，0.31 - 0.77，p = 0.002），因冠心病导致的SCD风险较低（OR 0.51；95% CI，0.32 - 0.82，p = 0.005），以及由非冠心病引起的SCD风险较低（OR 0.34；95% CI 0.13 - 0.90，p = 0.030）。
调节IL-18表达的IL-18启动子-137G/C多态性，是任何原因导致的SCD以及有无潜在冠心病患者SCD的重要预测指标。
