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在中国汉族人群中,ALOX15基因的两个单核苷酸多态性与冠状动脉疾病风险相关。

Two single nucleotide polymorphisms in ALOX15 are associated with risk of coronary artery disease in a Chinese Han population.

作者信息

Zhang Kai, Wang Yuan-yuan, Liu Qi-ji, Wang Hui, Liu Fang-fang, Ma Zhi-yong, Gong Yao-qin, Li Li

机构信息

Chinese Ministry of Education and Chinese Ministry of Public Health, Jinan, Shandong, China.

出版信息

Heart Vessels. 2010 Sep;25(5):368-73. doi: 10.1007/s00380-009-1223-5. Epub 2010 Jul 31.

Abstract

Arachidonate 12/15-lipoxygenase (12/15-LOX) has been implicated in the pathogenesis of atherosclerosis, but with contradicting results. The aim of this study was to investigate the association of two polymorphisms in ALOX15 and the risk of coronary artery disease (CAD) in a Chinese Han population. A total of 519 unrelated CAD patients and 608 unrelated control subjects of the Chinese Han population were recruited in the case-control study. Two tagSNPs, rs7217186:T>C and rs2619112:G>A, were selected and genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The carriers of the C allele (the CC homozygote and the CT heterozygote) of rs7217186:T>C and the carriers of the A allele (the AA homozygote and the GA heterozygote) of rs2619112:G>A displayed elevated odds ratios (ORs) for CAD compared with the TT homozygotes and GG homozygotes, respectively, after adjusting for other potential confounders including age, sex, body mass index, systolic blood pressure, diastolic blood pressure, glucose, triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and smoking status (adjusted odds ratio [OR] = 3.2, 95% confidence interval [CI]: 1.335-7.665, P = 0.009 and adjusted OR = 3.5, 95% CI: 1.343-9.330, P = 0.011). In stratified analyses, after adjusting those aforementioned confounders, the CC and CT genotypes of rs7217186:T>C were associated with a greater risk of CAD in subjects <60 years (adjusted OR = 5.7, 95% CI: 1.557-21.097, P = 0.009) and in females (adjusted OR = 9.3, 95% CI: 1.048-82.213, P = 0.045). For rs2619112:G>A, subjects (<60 years) carrying the A allele had a greater risk of CAD than the GG homozygotes (adjusted OR = 4.9, 95% CI: 1.215-19.547, P = 0.025); the male carriers of A allele also had a greater risk (adjusted OR = 3.5, 95% CI: 1.136-11.006, P = 0.029). In summary, the present study shows that after adjustment for other confounding CAD factors, rs7217186:T>C and rs2619112:G>A of ALOX15 are associated with increased risk of CAD in this Chinese Han population.

摘要

花生四烯酸12/15 -脂氧合酶(12/15 - LOX)与动脉粥样硬化的发病机制有关,但结果相互矛盾。本研究的目的是调查中国汉族人群中ALOX15基因的两个多态性与冠状动脉疾病(CAD)风险之间的关联。在病例对照研究中,共招募了519名无亲缘关系的中国汉族CAD患者和608名无亲缘关系的对照受试者。选择两个标签单核苷酸多态性(tagSNPs),即rs7217186:T>C和rs2619112:G>A,并通过聚合酶链反应-限制性片段长度多态性(PCR-RFLP)进行基因分型。在调整了包括年龄、性别、体重指数、收缩压、舒张压、血糖、甘油三酯、总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇和吸烟状况等其他潜在混杂因素后,rs7217186:T>C的C等位基因携带者(CC纯合子和CT杂合子)和rs2619112:G>A的A等位基因携带者(AA纯合子和GA杂合子)与CAD的优势比(OR)分别高于TT纯合子和GG纯合子(调整后的优势比[OR]=3.2,95%置信区间[CI]:1.335 - 7.665,P = 0.009;调整后的OR = 3.5,95% CI:1.343 - 9.330,P = 0.011)。在分层分析中,在调整上述混杂因素后,rs7217186:T>C的CC和CT基因型在<60岁的受试者(调整后的OR = 5.7,95% CI:1.557 - 21.097,P = 0.009)和女性(调整后的OR = 9.3,95% CI:1.048 - 82.213,P = 0.045)中与CAD风险增加相关。对于rs2619112:G>A,携带A等位基因的受试者(<60岁)患CAD的风险高于GG纯合子(调整后的OR = 4.9,95% CI:1.215 - 19.547,P = 0.025);A等位基因的男性携带者也有更高的风险(调整后的OR = 3.5,95% CI:1.136 - 11.006,P = 0.029)。总之,本研究表明,在调整其他混杂的CAD因素后,ALOX15基因的rs7217186:T>C和rs2619112:G>A与中国汉族人群中CAD风险增加相关。

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