BACKGROUND Single nucleotide polymorphisms (SNPs) in long non-coding RNA ANRIL (antisense noncoding RNA in the INK4 locus) were shown to be associated with coronary heart disease (CHD). The biological background for this association is not fully understood. The primary aim of this study was to investigate whether two leading ANRIL SNPs, namely, rs133049 and rs3217992, were associated with plasma levels of C-reactive protein among a large cohort of in-patients with CHD (n = 933). MATERIAL AND METHODS CHD was defined as previous or current detection of 50% stenosis of a main coronary artery. Severe periodontitis was diagnosed if proximal attachment loss of at least 5 mm was found in at least 30% of teeth. For genotyping rs1333049 we applied PCR using sequence-specific primers and for rs321799 restriction fragment length polymorphism analyses. C-reactive protein (CRP) plasma levels were determined using a particle-enhanced immunological turbidity test. In addition, interleukin (IL)-6, low-density lipoprotein (LDL), total cholesterol, high-density lipoprotein (HDL), triglycerides, and number of leukocytes were determined. RESULTS Genotype CC of rs1333049 was significantly associated with both elevated CRP levels and decreased HDL concentrations after univariate (p = 0.028, p = 0.012) and multivariate analysis (p = 0.041, p = 0.023) stratified for age, gender, body mass index, smoking, diabetes, and severe periodontitis. Furthermore, severe periodontitis (p = 0.031), but not SNP rs3217992, was associated with CRP plasma concentrations. CONCLUSIONS Among patients with CHD, ANRIL SNP rs1333049 is an independent risk indicator for both elevated CRP plasma levels and reduced HDL concentrations. ClinicalTrials.gov Identifier: NCT01045070.

中文翻译：

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ANRIL 多态性（rs1333049 和 rs3217992）与 CHD 住院患者血浆 CRP 水平的关系

背景 长非编码 RNA ANRIL（INK4 基因座中的反义非编码 RNA）中的单核苷酸多态性 (SNP) 被证明与冠心病 (CHD) 相关。这种关联的生物学背景尚不完全清楚。本研究的主要目的是调查两个主要的 ANRIL SNP，即 rs133049 和 rs3217992，是否与大量 CHD 住院患者（n = 933）的血浆 C 反应蛋白水平相关。材料和方法 CHD 被定义为以前或当前检测到的主冠状动脉 50% 狭窄。如果在至少 30% 的牙齿中发现至少 5 mm 的近端附着丧失，则诊断为严重牙周炎。为了对 rs1333049 进行基因分型，我们使用序列特异性引物进行 PCR，并进行 rs321799 限制性片段长度多态性分析。C 反应蛋白 (CRP) 血浆水平使用粒子增强免疫浊度测试确定。此外，还测定了白细胞介素 (IL)-6、低密度脂蛋白 (LDL)、总胆固醇、高密度脂蛋白 (HDL)、甘油三酯和白细胞数量。结果 在针对年龄、性别、体重指数、吸烟、糖尿病和严重的牙周炎。此外，严重牙周炎 (p = 0.031) 与 CRP 血浆浓度相关，但与 SNP rs3217992 无关。结论 在冠心病患者中，ANRIL SNP rs1333049 是 CRP 血浆水平升高和 HDL 浓度降低的独立风险指标。ClinicalTrials.gov 标识符：NCT01045070。