Keso T, Perola M, Laippala P, Ilveskoski E, Kunnas T A, Mikkelsson J, Penttilä A, Hurme M, Karhunen P J
Medical School, FIN-33014 University of Tampere, Tampere, Finland.
Atherosclerosis. 2001 Feb 15;154(3):691-7. doi: 10.1016/s0021-9150(00)00602-x.
Tumor necrosis factor (TNF) is an important cytokine in the inflammation process of atherosclerosis and is also involved in lipid metabolism. Two biallelic polymorphisms within TNF gene locus-TNFA at the position -308 in the promoter region of the TNF gene and TNFB in the first intron of the lymphotoxin-alpha (LT-alpha) have been reported to be associated with TNF production and with susceptibility to inflammatory diseases. We studied the association of these polymorphisms within the major histocompatibility complex (MHC) III region with coronary atherosclerosis and its manifestations. The autopsy series comprised 700 Caucasian Finnish men, aged 33-70 years (The Helsinki Sudden Death Study). Coronary stenosis and surface area of atherosclerotic changes (fatty streaks, fibrous plaques, complicated lesions and calcification) were measured and the presence of myocardial infarction and coronary thrombosis recorded. TNFA and TNFB genotypes were determined by the PCR-RFLP technique. The allele frequencies were TNFA1/TNFA2=0.88/0.12 and TNFB1/TNFB2=0.30/0.70. There was a strong linkage disequilibrium between the two polymorphisms. There were no differences in coronary stenosis and in the frequency of old or recent myocardial infarction or coronary thrombosis between men with different genotype status in either locus. Men with TNFA22 or TNFB11 genotype tended to have more fibrous lesions and calcification in their coronary arteries. TNFA and TNFB polymorphisms are unlikely to contribute to progression of atherosclerosis in a way clinically important.
肿瘤坏死因子（TNF）是动脉粥样硬化炎症过程中的一种重要细胞因子，也参与脂质代谢。据报道，TNF基因位点内的两个双等位基因多态性——TNF基因启动子区域-308位置的TNFA和淋巴毒素-α（LT-α）第一个内含子中的TNFB，与TNF产生及炎症性疾病易感性相关。我们研究了主要组织相容性复合体（MHC）III区域内这些多态性与冠状动脉粥样硬化及其表现的关联。尸检系列包括700名年龄在33 - 70岁的芬兰白人男性（赫尔辛基猝死研究）。测量冠状动脉狭窄程度和动脉粥样硬化病变的表面积（脂肪条纹、纤维斑块、复杂病变和钙化），并记录心肌梗死和冠状动脉血栓形成情况。通过PCR-RFLP技术确定TNFA和TNFB基因型。等位基因频率为TNFA1/TNFA2 = 0.88/0.12和TNFB1/TNFB2 = 0.30/0.70。这两个多态性之间存在强连锁不平衡。在两个位点具有不同基因型状态的男性之间，冠状动脉狭窄程度、陈旧性或近期心肌梗死或冠状动脉血栓形成的频率没有差异。具有TNFA22或TNFB11基因型的男性冠状动脉中往往有更多的纤维病变和钙化。TNFA和TNFB多态性不太可能以临床上重要的方式促进动脉粥样硬化进展。
