Vargas-Alarcón Gilberto, Posadas-Romero Carlos, Villarreal-Molina Teresa, Alvarez-León Edith, Angeles-Martinez Javier, Posadas-Sanchez Rosalinda, Monroy-Muñoz Irma, Luna-Fuentes Sergio, González-Salazar Carmen, Ramirez-Bello Julian, Cardoso-Saldaña Guillermo, Medina-Urrutia Aida, Kimura-Hayama Eric
1 Department of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez , Mexico City, Mexico .
J Interferon Cytokine Res. 2014 Sep;34(9):659-66. doi: 10.1089/jir.2013.0081. Epub 2014 Feb 19.
Coronary artery disease (CAD) is a multifactorial and polygenic disorder that results from an excessive inflammatory response. We analyzed whether interleukin-24 (IL-24) gene polymorphisms are associated with premature CAD in a case-control association study. Four polymorphisms (rs1150253, rs1150256, rs1150258, and rs3762344) of the IL-24 gene were analyzed by 5' exonuclease TaqMan genotyping assays in a group of 952 patients with premature CAD, 284 individuals with subclinical atherosclerosis (SA), and 912 controls. The studied polymorphisms were not associated with the risk of premature CAD or SA (P>0.05). Under dominant models adjusted for age, sex, body mass index, and medication, the polymorphisms were associated with cardiometabolic parameters and cardiovascular risk factors. Three polymorphisms (rs1150253, rs1150256, and rs3762344) were associated with hypertension and increased levels of systolic blood pressure in controls. In SA, 2 polymorphisms (rs1150256 and rs3762344) were associated with type 2 diabetes mellitus, gamma-glutamyl transpeptidase (GGT), and alkaline phosphatase, whereas rs1150253 was associated with GGT and type 2 diabetes mellitus and rs1150258 with GGT and alkaline phosphatase. In premature CAD, the 4 polymorphisms were associated with total cholesterol >200 mg/dL, low-density lipoprotein cholesterol (LDL-C), and GGT, whereas rs1150256 was associated also with ApoA. On the other hand, rs1150258 was associated with ApoA, LDL-C >100 mg/dL, and apoB/apoA ratio, and rs3762344 with ApoA, apoB/apoA ratio, LDL-C >100 mg/dL, and total cholesterol. On the basis of single-nucleotide polymorphism functional prediction software, rs1150253 and rs1150258 polymorphisms seem to be functional. The 4 studied polymorphisms were in linkage disequilibrium and had a similar haplotype distribution in patients and controls. Our study demonstrates the association of IL-24 polymorphisms with metabolic and cardiovascular risk factors in individuals with premature CAD, SA, and controls.
冠状动脉疾病(CAD)是一种由过度炎症反应导致的多因素和多基因疾病。在一项病例对照关联研究中,我们分析了白细胞介素-24(IL-24)基因多态性是否与早发性CAD相关。通过5'核酸外切酶TaqMan基因分型检测法,对952例早发性CAD患者、284例亚临床动脉粥样硬化(SA)个体和912例对照者进行了IL-24基因的4种多态性(rs1150253、rs1150256、rs1150258和rs3762344)分析。所研究的多态性与早发性CAD或SA的风险无关(P>0.05)。在根据年龄、性别、体重指数和用药情况进行调整的显性模型下,这些多态性与心脏代谢参数和心血管危险因素相关。三种多态性(rs1150253、rs1150256和rs3762344)与对照组的高血压和收缩压升高有关。在SA中,2种多态性(rs1150256和rs3762344)与2型糖尿病、γ-谷氨酰转肽酶(GGT)和碱性磷酸酶有关,而rs1150253与GGT和2型糖尿病有关,rs1150258与GGT和碱性磷酸酶有关。在早发性CAD中,这4种多态性与总胆固醇>200mg/dL、低密度脂蛋白胆固醇(LDL-C)和GGT有关,而rs1150256也与载脂蛋白A(ApoA)有关。另一方面,rs1150258与ApoA、LDL-C>100mg/dL和载脂蛋白B/载脂蛋白A比值有关,rs3762344与ApoA、载脂蛋白B/载脂蛋白A比值、LDL-C>100mg/dL和总胆固醇有关。根据单核苷酸多态性功能预测软件,rs1150253和rs1150258多态性似乎具有功能性。所研究的4种多态性处于连锁不平衡状态,在患者和对照者中具有相似的单倍型分布。我们的研究证明了IL-24多态性与早发性CAD、SA个体及对照者的代谢和心血管危险因素之间的关联。