Association between genetic variants in the Coenzyme Q 10metabolism and Coenzyme Q10status in humans

Abstract

Abstract. Background: Coenzyme Q10(CoQ10) is essential for mitochondrial energy production and serves as an antioxidants in extra mitochondrial membranes. The genetics of primary CoQ 10deficiency has been described in several studies, whereas the influence of common genetic variants on CoQ10status is largely unknown. Here we tested for non-synonymous single-nucleotidepolymorphisms (SNP) in genes involved in the biosynthesis (CoQ3G272S , CoQ6 M406V, CoQ7M103T), reduction (NQO1P187S, NQO2L47F) and metabolism (apoE3/4) of CoQ10and their association with CoQ10status. For this purpose, CoQ10serum 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. Findings. At T0, the CoQ10level of heterozygous NQO1P187S carriers were significantly lower than homozygous S/S carriers (0.93 0.25 M versus 1.34 0.42 M, p = 0.044). For this polymorphism a structure homology-based method (PolyPhen) revealed a possibly damaging effect on NQO1 protein activity. Furthermore, CoQ10plasma levels were significantly increased in apoE4/E4 genotype after supplementation in comparison to apoE2/E3 genotype (5.93 0.151 M versus 4.38 0.792 M, p = 0.034). Likewise heterozygous CoQ3G272S carriers had higher CoQ 10plasma levels at T14compared to G/G carriers but this difference did not reach significance (5.30 0.96 M versus 4.42 1.67 M, p = 0.082). Conclusions: In conclusion, our pilot study provides evidence that NQO1P187S and apoE polymorphisms influence CoQ10status in humans. © 2011 Döring et al; licensee BioMed Central Ltd.