C-reactive protein levels and common polymorphisms of the interleukin-1 gene cluster and interleukin-6 gene in patients with coronary heart disease
C-reactive protein levels and common polymorphisms of the interleukin-1 gene cluster and interleukin-6 gene in patients with coronary heart disease
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DOI：
10.1111/j.1365-2370.2004.00476.x
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发表时间：
2004-10-01
期刊：
影响因子：
--
通讯作者：
Kalnins, U
中科院分区：
文献类型：
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作者：
Latkovskis, G;Licis, N;Kalnins, U
C反应蛋白（CRP）是一种与心血管风险增加相关的炎症标志物。CRP的产生受白细胞介素（IL）-1 β、IL-1受体拮抗剂和IL-6的调节。在160例经冠状动脉造影证实的冠心病（CHD）患者中，我们检测了编码这些细胞因子的5个基因多态性：IL-1B（-511）、IL-1B（+3954）、IL-1 RN内含子2可变数目串联重复序列（VNTR）多态性[IL-1 RN（VNTR）]、IL-6（-174）和IL-6（-572）与CRP水平的关系。CRP值经对数标准化（log-CRP）进行统计学计算。在单变量分析中，IL-1B（+3954）T等位基因和IL-1 RN（VNTR）等位基因2 [IL-1 RN（VNTR）*2]的携带状态分别与较高（P < 0.01）和较低（P < 0.05）log-CRP值相关。在分析的潜在混杂因素中，吸烟、体重指数、总胆固醇（P均< 0.05）和糖尿病（P = 0.056）与CRP水平呈正相关。校正非遗传协变量后，CRP水平仍显著高于对照组。IL-1B（+3954）T携带者高于非携带者（P < 0.01）：平均log-CRP（95%置信区间）为0.443（0.311-0.574）与CC基因型的0.240（0.107-0.373）相比，其对应于反转换的CRP水平分别为2.77和1.74 mg l（-1）。IL-1 RN（VNTR）*2的校正相关性也很显著（P < 0.01），等位基因2存在时CRP水平较低：携带者的平均log-CRP值为0.252（0.115-0.388），非携带者为0.421（0.290-0.552）（CRP分别为1.79和2.64 mg l（-1））。当两种多态性的等位基因同时进入模型时，IL-1B（+3954）T的相关性仍然显著（P < 0.05），但IL-1 RN（VNTR）*2的相关性不显著。我们得出结论，IL-1B（+3954）T与CHD患者的CRP水平升高相关，我们发现在调整主要危险因素后，这种相关性是显著的。我们的数据还表明，IL-1 RN（VNTR）*2与同一患者中较低的CRP水平可能存在相关性。
C-reactive protein (CRP) is an inflammatory marker associated with increased cardiovascular risk. Production of CRP is regulated by interleukin (IL)-1beta, IL-1 receptor antagonist and IL-6. In 160 patients with coronary heart disease (CHD) confirmed by angiography, we examined the relationship between CRP level and five polymorphisms in genes coding for these cytokines: IL-1B(-511), IL-1B(+3954), a variable number tandem repeat (VNTR) polymorphism in intron 2 of IL-1RN [IL-1RN(VNTR)], IL-6(-174) and IL-6(-572). CRP values were logarithmically normalized (log-CRP) for statistical calculations. In univariate analysis, carrier status for the IL-1B(+3954)T allele and IL-1RN(VNTR) allele 2 [IL-1RN(VNTR)*2] correlated with higher (P < 0.01) and lower (P < 0.05) log-CRP values, respectively. Among the potential confounding factors analysed, smoking, body mass index, total cholesterol (P < 0.05 for all) and diabetes (P = 0.056) were positively correlated with CRP level. After adjustment for non-genetic covariates, CRP levels remained significantly (P < 0.01) higher in carriers of IL-1B(+3954)T than in non-carriers: mean log-CRP (with 95% confidence interval) was 0.443 (0.311-0.574) for CT or TT genotypes compared with 0.240 (0.107-0.373) for the CC genotype, which corresponded to back-transformed CRP levels of 2.77 and 1.74 mg l(-1), respectively. Adjusted association was also significant for IL-1RN(VNTR)*2 (P < 0.01), with lower CRP levels in the presence of allele 2: the mean log-CRP value was 0.252 (0.115-0.388) for carriers and 0.421 (0.290-0.552) for non-carriers (CRP 1.79 and 2.64 mg l(-1), respectively). When alleles of both polymorphisms were entered into the model simultaneously, the association remained significant for IL-1B(+3954)T (P < 0.05), but not for IL-1RN(VNTR)*2. We conclude that IL-1B(+3954)T is associated with higher CRP levels in patients with CHD, and we found that this association was significant after adjustment for major risk factors. Our data also suggest a possible relationship of IL-1RN(VNTR)*2 with lower CRP levels in the same patients.