Tobacco smoking, estrogen receptor alpha gene variation and small low density lipoprotein level.
Tobacco smoking, estrogen receptor alpha gene variation and small low density lipoprotein level.
复制标题
吸烟、雌激素受体α基因变异和低密度脂蛋白水平小。
DOI：
10.1093/hmg/ddi242
复制
发表时间：
2005
影响因子：
3.5
通讯作者：
Housman,DavidE
中科院分区：
文献类型：
--
作者：
Shearman,AmandaM;Demissie,Serkalem;Cupples,LAdrienne;Peter,Inga;Schmid,ChristopherH;Ordovas,JoseM;Mendelsohn,MichaelE;Housman,DavidE
高水平的小低密度脂蛋白（LDL）颗粒是心血管发病率和死亡率的主要危险因素。雌激素和吸烟都具有已知的抗雌激素作用，可改变致动脉粥样硬化的脂质谱。我们测试了吸烟和雌激素受体α基因（ESR1）变异之间的相互作用与动脉粥样硬化小LDL颗粒的血浆浓度和LDL颗粒大小的关系。我们研究了1727名不相关的受试者，854名女性和873名男性，平均年龄51岁（SD 10），来自基于人群的Framingham心脏研究。协变量调整后，吸烟并具有commonESR1 c.454-397 tt基因型的女性（在30%的女性中，在2外显子开始前的两条染色体397位置上都存在tt基因型）的小LDL颗粒水平比具有其他基因型的女性高1.7倍（吸烟-基因型相互作用的p值为0.001）。包括c在内的其他三个esr1变异也获得了类似的结果。454-351A >G，在同一连杆不平衡块。在第4外显子的一个单独的连锁不平衡区（P=0.003）中，第五种变异也有类似的实质性性别特异性结果（P=0.003）。吸烟和具有特定、普通基因型的女性具有明显较高的致动脉粥样硬化小LDL颗粒的血浆浓度。重要的结果显示吸烟的剂量依赖效应，在绝经前和绝经后妇女中都很明显。报道的关联有可能解释某些女性使用雌激素的相关风险，以及最近报道的包含ofc的anesr1单倍型之间的关联。454-397与心肌梗死和缺血性心脏病增加相关的454 - 351等位基因，独立于标准，确定心血管危险因素。
High levels of small low density lipoprotein (LDL) particles are a major risk factor for cardiovascular morbidity and mortality. Both estrogens and smoking, with known anti-estrogenic effects, alter the atherogenic lipid profile. We tested for a role of interaction between smoking and estrogen receptor α gene(ESR1)variation in association with plasma concentration of atherogenic small LDL particles and LDL particle size. We studied 1727 unrelated subjects, 854 women and 873 men, mean age 51 years (SD 10), from the population-based Framingham Heart Study. After covariate adjustment, women who smoked and had the commonESR1 c.454-397 TTgenotype (in 30% of women,Twas present on both chromosomes at position 397 prior to the start of exon 2) had >1.7-fold higher levels of small LDL particles than women with the alternative genotypes (P-value for smoking–genotype interaction was 0.001). Similar results were obtained for three otherESR1variants includingc.454–351A>G, in the same linkage disequilibrium block. A similar substantial gender-specific result was also evident with a fifth variant, in a separate linkage disequilibrium block, in exon 4 (P=0.003). Women who smoked and had specific, commonESR1genotypes had a substantially higher plasma concentration of atherogenic small LDL particles. Significant results revealed a dose-dependent effect of smoking and were evident in both pre- and postmenopausal women. The reported association has the potential to explain the risks associated with estrogen use in certain women and a recent report of association between anESR1haplotype comprised ofc.454–397 Tandc.454–351 Aalleles with increased myocardial infarction and ischaemic heart disease, independent of the standard, established cardiovascular risk factors.