Department of Cardiology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Chin Med J (Engl). 2011 Jan;124(1):66-71. doi: 10.3901/jme.2011.08.066.
Susceptibility to coronary artery disease (CAD) and diabetes is encoded by distinct, tightly-linked single nucleotide polymorphisms on chromosome 9p21. This study aimed to examine the association of variant rs1333049 on chromosome 9p21.3 with early-onset and severity of CAD in Chinese patients with and without type 2 diabetes, and to determine the possible impact of rs1333049 on glucose metabolism and inflammation pathways.
Genotyping of variant rs1333049 on chromosome 9p21.3 was performed in 2387 patients with and without diabetes who were undergoing coronary angiography to evaluate suspected or established CAD. Serum levels of glucose, glycosylated hemoglobin A(1c) (HbA(1c)), insulin, high-sensitivity C-reactive protein, tumor necrosis factor-α, and interleukin-6 were also measured, and compared with each patient's genotype.
The homozygous CC genotype of rs1333049 was significantly associated with CAD in diabetic (OR: 1.270, P = 0.044) and non-diabetic (OR: 1.369, P = 0.011) patients after adjusting for traditional risk factors. There was an association between CC genotype and number of diseased vessels in diabetics (P = 0.019), but not in non-diabetics (P = 0.126). Among diabetic patients, CC genotype carriers had an increased risk of early-onset CAD (OR: 2.367, P = 0.008) and greater cumulative atherosclerotic burden compared with non-CC genotype carriers (Gensini score: 31.80 ± 17.20 vs. 23.09 ± 21.63, P = 0.039). No significant differences were observed between genotypes of rs1333049 in serum levels of glucose, insulin, HbA(1c), or inflammatory cytokines for diabetic or non-diabetic patients with CAD.
This study demonstrated a significant association of rs1333049 polymorphism on chromosome 9p21.3 with CAD in Chinese diabetic and non-diabetic patients. The homozygous CC genotype of rs1333049 confers a magnified risk of early-onset and more severe CAD in diabetic patients through a novel biological pathway unrelated to glucose metabolism or inflammation.
冠心病（CAD）和糖尿病的易感性由染色体 9p21 上不同的、紧密连锁的单核苷酸多态性编码。本研究旨在研究染色体 9p21.3 上的变体 rs1333049 与中国有或无 2 型糖尿病的早发和 CAD 严重程度的相关性，并确定 rs1333049 对葡萄糖代谢和炎症途径的可能影响。
对 2387 名接受冠状动脉造影以评估疑似或确诊 CAD 的有或无糖尿病患者进行染色体 9p21.3 上变体 rs1333049 的基因分型。还测量了每位患者的基因型与血清葡萄糖、糖化血红蛋白 A1c（HbA1c）、胰岛素、高敏 C 反应蛋白、肿瘤坏死因子-α 和白细胞介素-6 水平，并进行了比较。
rs1333049 的纯合 CC 基因型在调整传统危险因素后，与糖尿病（OR：1.270，P = 0.044）和非糖尿病（OR：1.369，P = 0.011）患者的 CAD 显著相关。在糖尿病患者中，CC 基因型与病变血管数量相关（P = 0.019），但在非糖尿病患者中不相关（P = 0.126）。在糖尿病患者中，CC 基因型携带者发生早发 CAD 的风险增加（OR：2.367，P = 0.008），与非 CC 基因型携带者相比，累积动脉粥样硬化负担更大（Gensini 评分：31.80±17.20 比 23.09±21.63，P = 0.039）。在有 CAD 的糖尿病或非糖尿病患者中，rs1333049 基因型在血清葡萄糖、胰岛素、HbA1c 或炎症细胞因子水平上无显著差异。
本研究表明，染色体 9p21.3 上 rs1333049 多态性与中国糖尿病和非糖尿病患者的 CAD 显著相关。rs1333049 的纯合 CC 基因型通过与葡萄糖代谢或炎症无关的新的生物学途径，增加了糖尿病患者早发和更严重 CAD 的风险。
