体力活动可改变多种HDL-修饰基因的效果

Physical Activity Alters Effects of Various HDL-Modifying Genes

体力活动可改变多种HDL-修饰基因的效果

March 4, 2011 — Common genetic variants that are linked with HDL-cholesterol levels are modified by physical-activity levels, according to the results of a new study [1]. The effects of common variations in the hepatic lipase (LIPC) and cholesteryl ester-transfer protein (CETP) genes on HDL-cholesterol levels were larger among active women, whereas the opposite was observed for a common variant in the lipoprotein lipase (LPL) gene, with the effects on HDL-cholesterol largest among less active women, report investigators.

2011年3月4日 –根据一项新的研究结果，常见的基因突变与高密度脂蛋白胆固醇水平的相关性受体力活动水平的影响。研究人员报告，肝脂酶（LIPC）和胆固醇酯转移蛋白（CETP）基因常见变异对高密度脂蛋白胆固醇水平的影响在体力活动较多的女性中较大，相反，脂蛋白脂肪酶（LPL）基因的常见变异，对高密度脂蛋白胆固醇的影响大多在体力活动不活跃的妇女中。

Senior investigator Dr (Brigham and Women's Hospital, Boston, MA) told heartwire : "Exercising really has an important impact on HDL cholesterol. Recently, too, there are new genetic loci identified that affect HDL-cholesterol levels. The question is, how do these two factors work together, or work against one another, to alter HDL-cholesterol levels?"

高级研究员Brendan Everett博士（马萨诸塞州波士顿Brigham和女子医院）告诉heartwire：“锻炼真的对高密度脂蛋白胆固醇具有重要影响。最近也发现了新的基因位点可以影响高密度脂蛋白胆固醇水平。问题是，这两个因素是如何协同作用，或相互拮抗，改变高密度脂蛋白胆固醇水平的？”

Lead investigator Dr Tariq Ahmad (Duke University Medical Center, Durham, NC)suggested the results might partly explain why some patients have larger increases in HDL-cholesterol levels in response to exercise compared with others who might not receive quite the same bump. He said： "Our findings suggest that some of this variability is related to the way exercise interacts with genes known to affect HDL-cholesterol levels."

主要研究者Tariq Ahmad博士（杜克大学医学中心）认为这个研究结果或许可以部分解释为什么与其他患者相比，一些患者在锻炼后高密度脂蛋白胆固醇有较大的升幅。他说：“我们的研究结果表明，一些这种变异与一致的可影响高密度脂蛋白胆固醇水平的基因相关。”
In this prospective cohort study of 22939 healthy women of European ancestry taking part in the Women's Health Study (WHS), published in the February 2011 issue of Circulation: Cardiovascular Genetics, the researchers first selected 58 single nucleotide polymorphisms (SNPs) in nine genes that showed a genomewide association with HDL-cholesterol levels and then attempted to determine whether these genetic variations were modified by physical activity. The group identified seven SNPs on three loci whose effects on HDL cholesterol were modified by physical activity. The strongest evidence was observed for SNPs at LPL, LIPC, and CETP, genes that have been linked with HDL cholesterol in previous studies.

在这22 939欧洲血统的健康妇女前瞻性参加了妇女健康研究（WHS）在2011年2月流通出版发行，部分的研究：心血管遗传学，研究人员首先选取九个基因58个单核苷酸多态性（SNPs）这表现出与高密度脂蛋白胆固醇水平的基因关联，然后试图确定这些遗传变异是由身体活​​动修改。工作组确定的三个位点的高密度脂蛋白胆固醇对身体活动是由改性七单核苷酸多态性。最有力的证据是在脂​​酶观察，LIPC，和胆固醇酯转运蛋白单核苷酸多态性，已与高密度脂蛋白胆固醇在以往的研究与基因。

The researchers noted that the effects of the gene variants on HDL cholesterol varied according to the level of physical activity. In active individuals--active defined as exerting more than 8.8 MET-hours/week--the increases in HDL cholesterol per copy of the minor-allele increases for LIPC and CETP were larger than in those who exercised less frequently. The reverse, however, was observed with LPL.

研究人员指出，基因变异对高密度脂蛋白胆固醇的效应随体力活动的水平而变化。与较少锻炼的个体相比，体力活动较多的个体（体力活动较多的定义是每周至少8.8小时）LIPC和CETP等位基因每增加1拷贝，高密度脂蛋白胆固醇即可见明显增加。相反，LPL.的影响正好相反。
"For some reason, this common variation in LPL, which tends to increase your HDL-cholesterol level, increased the HDL-cholesterol levels more in women who were inactive than in women who were active," said Everett. "It's a little counterintuitive."

“由于某些原因，LPL中的这种常见变异（可增加高密度脂蛋白胆固醇水平），与体力活动较多的女性相比，在体力活动较少的女性中可更多的增加高密度脂蛋白胆固醇的水平” Everett说。“这有点违反直觉。”

Among women with at least one copy of the minor allele at the LPL SNP, there was a reduced risk of MI only in active women, and not in those who exercised less frequently. On the other hand, minor-allele carrier status of the CETP variant was associated with a reduced risk of MI regardless of activity levels. No association was observed between LIPC SNP carrier status and MI risk.

在至少有一个LPL单核苷酸多态性等位基因的妇女中，仅在体力活动较多的女性中可减少心肌梗死的风险，而在那些体力活动较少的女性中未见此差异。另一方面，无论体力活动水平如何，CETP变异微小等位基因携带状态与心肌梗死的风险减少相关。LIPC单核苷酸多态性携带状态和心肌梗死的风险未观察到相关性。

"One of the more interesting things that we saw, and this needs to be replicated and validated in other cohorts, is that there appears to be an interaction between physical-activity levels and your genetic makeup at the LPL gene and your risk of myocardial infarction," Everett told heartwire . "If you have a copy of the beneficial allele of CETP, your risk of having a heart attack is reduced, regardless of whether you exercise a lot or exercise a little. That's great, but it doesn't seem to be the case for the mutation in LPL. If you have the beneficial allele at LPL--and we presume it would be beneficial because it increases HDL cholesterol--it's a benefit only if you exercise. If you don't exercise, it's kind of a wash."

“更有趣的是（这需要在其他队列研究中重复确认）在体力活动水平和LPL基因构成及心肌梗死的风险之间存在相互作用” Everett 告诉heartwire。 “如果你有一个拷贝CETP有益的等位基因，你患心脏时间的风险会降低，无论你锻炼多还是少。这非常好，但对于LPL突变却不如此。如果你有LPL有益的等位基因（我们假设它是有益的，因为它可增加高密度脂蛋白胆固醇的水平），仅在你锻炼的时候是有益的。如果你不锻炼，它会没有丝毫作用。”

Circ Cardiovasc Genet 2011; 4: 74-80.