Association between genetic variants in the Coenzyme Q(10 )metabolism and Coenzyme Q(10 )status in humans

BACKGROUND: Coenzyme Q(10 )(CoQ(10)) is essential for mitochondrial energy production and serves as an antioxidants in extra mitochondrial membranes. The genetics of primary CoQ(10 )deficiency has been described in several studies, whereas the influence of common genetic variants on CoQ(10 )status is largely unknown. Here we tested for non-synonymous single-nucleotidepolymorphisms (SNP) in genes involved in the biosynthesis (CoQ3(G272S ), CoQ6(M406V), CoQ7(M103T)), reduction (NQO1(P187S), NQO2(L47F)) and metabolism (apoE3/4) of CoQ(10 )and their association with CoQ(10 )status. For this purpose, CoQ(10 )serum levels of 54 healthy male volunteers were determined before (T(0)) and after a 14 days supplementation (T(14)) with 150 mg/d of the reduced form of CoQ(10). FINDINGS: At T(0), the CoQ(10 )level of heterozygous NQO1(P187S )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, CoQ(10 )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 CoQ3(G272S )carriers had higher CoQ(10 )plasma levels at T(14 )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). CONCLUSIONS: In conclusion, our pilot study provides evidence that NQO1(P187S )and apoE polymorphisms influence CoQ(10 )status in humans.