Jang Yangsoo, Chae Jey Sook, Hyun Yae Jung, Koh Soo Jeong, Kim Ji Young, Ko Min Ji, Rim Se-Joong, Shin Hyun-Joon, Ordovas Jose M, Lee Jong Ho
Cardiovascular Genome Center, Cardiovascular Hospital, Severance Hospital, Sinchon-dong, Seodaemun-gu, Seoul, South Korea.
Clin Sci (Lond). 2007 Oct;113(8):349-56. doi: 10.1042/CS20070014.
In the present study we investigated the association of the RANTES (regulated upon activation, normal T-cell expressed and secreted) -28C>G and -403G>A promoter polymorphisms with the concentration of serum RANTES and CAD (coronary artery disease) in Korean men. We included 553 male CAD patients with (n=176) or without (n=377) Type 2 diabetes, aged 40-65 years with previous myocardial infarction ( approximately 50%) or angiographically confirmed CAD ( approximately 50%), and 416 aged-matched healthy male controls. The main outcome measures were the OR (odds ratio) of CAD risk and the serum RANTES concentration evaluated by sandwich ELISA. Although the RANTES -28C>G genotype had no significant association with CAD risk, the presence of the minor allele of the RANTES -403G>A single nucleotide polymorphism was associated with a lower risk of CAD {OR 0.70 [95% CI (confidence interval) 0.54-0.92], P=0.011} after adjusting for age, BMI (body mass index), cigarette smoking and alcohol consumption. Serum RANTES concentrations were significantly associated with the -403G>A genotype in controls (G/G: 44.7+/-3.3 ng/ml, G/A: 36.5+/-2.0 ng/ml, A/A: 28.7+/-2.5 ng/ml; P<0.001), non-diabetic CAD patients (G/G: 50.9+/-3.0 ng/ml, G/A: 42.2+/-2.6 ng/ml, A/A: 41.3+/-4.4 ng/ml; P<0.05) and diabetic CAD patients (G/G: 58.5+/-3.5 ng/ml, G/A: 49.6+/-4.1 ng/ml, A/A: 42.2+/-4.3 ng/ml; P<0.05); however, such associations were not observed in the subgroup of CAD patients taking lipid-lowering medication. Moreover, serum RANTES was positively correlated with C-reactive protein (r=0.289, P<0.001) and platelet counts (r=0.253, P<0.001). The results of the present study demonstrate that the RANTES -403A allele is associated with lower serum RANTES concentrations and consequently with reduced CAD risk.
在本研究中,我们调查了韩国男性中调节激活正常T细胞表达和分泌因子(RANTES)-28C>G和-403G>A启动子多态性与血清RANTES浓度及冠状动脉疾病(CAD)之间的关联。我们纳入了553例男性CAD患者,其中有2型糖尿病的患者176例,无2型糖尿病的患者377例,年龄在40 - 65岁之间,既往有心肌梗死(约50%)或经血管造影证实患有CAD(约50%),以及416例年龄匹配的健康男性对照。主要观察指标为CAD风险的比值比(OR)和通过夹心酶联免疫吸附测定法评估的血清RANTES浓度。尽管RANTES -28C>G基因型与CAD风险无显著关联,但在调整年龄、体重指数(BMI)、吸烟和饮酒因素后,RANTES -403G>A单核苷酸多态性的次要等位基因的存在与较低的CAD风险相关{OR 0.70 [95%置信区间(CI)0.54 - 0.92],P = 0.011}。血清RANTES浓度与对照组(G/G:44.7±3.3 ng/ml,G/A:36.5±2.0 ng/ml,A/A:28.7±2.5 ng/ml;P < 0.001)、非糖尿病CAD患者(G/G:50.9±3.0 ng/ml,G/A:42.2±2.6 ng/ml,A/A:41.3±4.4 ng/ml;P < 0.05)和糖尿病CAD患者(G/G:58.5±3.5 ng/ml,G/A:49.6±4.1 ng/ml,A/A:42.2±4.3 ng/ml;P < 0.05)的-403G>A基因型显著相关;然而,在服用降脂药物的CAD患者亚组中未观察到此类关联。此外,血清RANTES与C反应蛋白呈正相关(r = 0.289,P < 0.001),与血小板计数呈正相关(r = 0.253,P < 0.001)。本研究结果表明,RANTES -403A等位基因与较低的血清RANTES浓度相关,因此与降低的CAD风险相关。