Department of Internal Medicine, The Catholic University of Korea, School of Medicine, and the Research Institute of Immunobiology, The Catholic University of Korea, Gyeonggi-do, Korea.
J Rheumatol. 2013 Jun;40(6):798-808. doi: 10.3899/jrheum.120954. Epub 2013 Apr 15.
Dyslipidemia, a risk factor for cardiovascular diseases, is more prevalent in patients with rheumatoid arthritis (RA) than in the general population. We investigated whether single-nucleotide polymorphisms (SNP) modulating low-density lipoprotein (LDL) cholesterol affect susceptibility, severity, and progression of RA.
We enrolled 302 patients with RA and 1636 healthy controls, and investigated the SNP modulating LDL cholesterol. Clinical characteristics of RA, serum adipocytokine concentrations, and radiographic severity were analyzed according to genotype score based on the number of unfavorable alleles. The influence of genotype score on radiographic progression was also investigated using multivariable logistic models.
We identified 3 SNP (rs688, rs693, and rs4420638) modulating LDL cholesterol in Koreans, which correlated well with LDL cholesterol levels in both patients with RA and controls. Among them, 2 SNP, rs688 and rs4420638, were more prevalent in patients with RA than in controls. In patients with RA carrying more unfavorable alleles (genotype score ≥ 3), disease activity measures, serum adipocytokine levels, and radiographic severity were all increased. The genotype score was an independent risk factor for radiographic progression of RA over 2 years, and its effect was greater than the influence of conventional risk factors.
SNP modulating LDL cholesterol influence the risk, activity, and severity of RA. These results provide the first evidence that genetic mechanisms linked to dyslipidemia may directly contribute to the susceptibility and prognosis of RA, a representative of chronic inflammatory diseases, explaining the high incidence of dyslipidemia in RA.
血脂异常是心血管疾病的危险因素，在类风湿关节炎（RA）患者中比普通人群更为普遍。我们研究了调节低密度脂蛋白（LDL）胆固醇的单核苷酸多态性（SNP）是否会影响 RA 的易感性、严重程度和进展。
我们纳入了 302 例 RA 患者和 1636 例健康对照者，并研究了调节 LDL 胆固醇的 SNP。根据不利等位基因的数量，基于基因型评分分析了 RA 的临床特征、血清脂肪细胞因子浓度和放射学严重程度。还使用多变量逻辑模型研究了基因型评分对放射学进展的影响。
我们在韩国人群中发现了 3 个调节 LDL 胆固醇的 SNP（rs688、rs693 和 rs4420638），它们与 RA 患者和对照组的 LDL 胆固醇水平密切相关。其中，rs688 和 rs4420638 这 2 个 SNP 在 RA 患者中比在对照组中更为常见。在携带更多不利等位基因（基因型评分≥3）的 RA 患者中，疾病活动度指标、血清脂肪细胞因子水平和放射学严重程度均增加。基因型评分是 RA 放射学进展 2 年的独立危险因素，其作用大于传统危险因素的影响。
调节 LDL 胆固醇的 SNP 影响 RA 的风险、活动度和严重程度。这些结果首次提供了证据，表明与血脂异常相关的遗传机制可能直接导致 RA 的易感性和预后，RA 是慢性炎症性疾病的代表，解释了 RA 中血脂异常发生率高的原因。
