Fischer Alexandra, Schmelzer Constance, Rimbach Gerald, Niklowitz Petra, Menke Thomas, Döring Frank
Institute of Human Nutrition and Food Science, Devision of Molecular Prevention, Christian-Albrechts-University of Kiel, Heinrich-Hecht-Platz 10, 24118 Kiel, Germany.
BMC Res Notes. 2011 Jul 21;4:245. doi: 10.1186/1756-0500-4-245.
Coenzyme Q10 (CoQ10) is essential for mitochondrial energy production and serves as an antioxidants in extra mitochondrial membranes. The genetics of primary CoQ10 deficiency has been described in several studies, whereas the influence of common genetic variants on CoQ10 status is largely unknown. Here we tested for non-synonymous single-nucleotidepolymorphisms (SNP) in genes involved in the biosynthesis (CoQ3G272S , CoQ6M406V, CoQ7M103T), reduction (NQO1P187S, NQO2L47F) and metabolism (apoE3/4) of CoQ10 and their association with CoQ10 status. For this purpose, CoQ10 serum levels of 54 healthy male volunteers were determined before (T0) and after a 14 days supplementation (T14) with 150 mg/d of the reduced form of CoQ10.
At T0, the CoQ10 level of heterozygous NQO1P187S carriers were significantly lower than homozygous S/S carriers (0.93 ± 0.25 μM versus 1.34 ± 0.42 μM, p = 0.044). For this polymorphism a structure homology-based method (PolyPhen) revealed a possibly damaging effect on NQO1 protein activity. Furthermore, CoQ10 plasma levels were significantly increased in apoE4/E4 genotype after supplementation in comparison to apoE2/E3 genotype (5.93 ± 0.151 μM versus 4.38 ± 0.792 μM, p = 0.034). Likewise heterozygous CoQ3G272S carriers had higher CoQ10 plasma levels at T14 compared to G/G carriers but this difference did not reach significance (5.30 ± 0.96 μM versus 4.42 ± 1.67 μM, p = 0.082).
In conclusion, our pilot study provides evidence that NQO1P187S and apoE polymorphisms influence CoQ10 status in humans.
辅酶Q10（CoQ10）对于线粒体能量产生至关重要，并在线粒体外膜中作为抗氧化剂发挥作用。几项研究已经描述了原发性CoQ10缺乏症的遗传学情况，而常见基因变异对CoQ10状态的影响在很大程度上尚不清楚。在此，我们检测了参与CoQ10生物合成（CoQ3G272S、CoQ6M406V、CoQ7M103T）、还原（NQO1P187S、NQO2L47F）和代谢（载脂蛋白E3/4）的基因中的非同义单核苷酸多态性（SNP）及其与CoQ10状态的关联。为此，测定了54名健康男性志愿者在每日补充150mg还原型CoQ10前（T0）和补充14天后（T14）的CoQ10血清水平。
在T0时，NQO1P187S杂合子携带者的CoQ10水平显著低于纯合子S/S携带者（0.93±0.25μM对1.34±0.42μM，p = 0.044）。对于这种多态性，一种基于结构同源性的方法（PolyPhen）显示对NQO1蛋白活性可能有损害作用。此外，与载脂蛋白E2/E3基因型相比，补充后载脂蛋白E4/E4基因型的CoQ10血浆水平显著升高（5.93±0.151μM对4.38±0.792μM，p = 0.034）。同样，与G/G携带者相比，CoQ3G272S杂合子携带者在T14时的CoQ10血浆水平更高，但这种差异未达到显著水平（5.30±0.96μM对4.42±1.67μM，p = 0.082）。
总之，我们的初步研究提供了证据，表明NQO1P187S和载脂蛋白E多态性会影响人类的CoQ10状态。
