Hubacek Jaroslav A, Adamkova Vera, Zlatohlavek Lukas, Steiner-Mrazova Lenka, Vrablik Michal
Department of Experimental Medicine, Institute for Clinical and Experimental Medicine, IKEM-CEM, Videnska 1958/9, 140 21 Prague 4, Czech Republic, Phone: +420 261 363 379, Fax: +420 241 721 574.
Department of Preventive Cardiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Drug Metab Pers Ther. 2017 Dec 20;32(4):177-182. doi: 10.1515/dmpt-2017-0027.
The gene COQ2, encoding 4-hydroxybenzoate-polyprenyltransferase (coenzyme Q2), belongs to the candidates potentially influencing statin treatment tolerability. This enzyme is involved in the biosynthesis of coenzyme Q10 (CoQ10), in which depletion induced by statin treatment is implicated in the development of statin-associated muscle symptoms (SAMS). Thus, polymorphisms in the COQ2 gene might explain susceptibility to SAMS.
Adult patients with SAMS (on low doses of atorvastatin and simvastatin)-induced myalgia/myopathy (n=278), patients on statins but without SAMS (n=293) and population (part of the post-MONICA [Multinational MONItoring of trends and determinants in CArdiovascular disease] study) controls (n=561) were genotyped (polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP] assay) for rs6535454 and rs4693075 polymorphisms within the COQ2 gene loci.
Distribution of rs6535454 in patients with SAMS (GG=51.1%, GA=40.0%, AA=8.9%) did not significantly differ (p=0.33; respectively 0.32 for codominant models of the analysis) from that in the population controls (GG=48.1%, GA=45.0%, AA=6.9%) or the SAMS-unaffected patients (GG=49.8%, GA=40.3%, AA=9.7%). Similarly, neither rs4693075 was associated with SAMS (CC=36.8%, CG=48.2%, GG=15.0% in patients suffering SAMS vs. CC=36.6%, CG=47.5%, GG=15.9 in controls and CC=35.8%, CG=48.2%, GG=15.9% in symptom-free patients, p=0.94 and 0.95 for codominant models of the analysis). Also, the haplotype distributions were not significantly different between the groups analyzed.
The polymorphisms of the COQ2 gene do not associate with SAMS in the Czech patients treated with low doses of statins. This is another clue that the coenzyme Q10 pathway is not the most important for the development of SAMS.
编码4-羟基苯甲酸-聚异戊二烯基转移酶（辅酶Q2）的COQ2基因属于可能影响他汀类药物治疗耐受性的候选基因。该酶参与辅酶Q10（CoQ10）的生物合成，他汀类药物治疗引起的CoQ10耗竭与他汀类药物相关肌肉症状（SAMS）的发生有关。因此，COQ2基因多态性可能解释对SAMS的易感性。
对患有SAMS（服用低剂量阿托伐他汀和辛伐他汀）引起的肌痛/肌病的成年患者（n = 278）、服用他汀类药物但无SAMS的患者（n = 293）以及人群（心血管疾病趋势和决定因素多国监测[MONICA]研究的一部分）对照（n = 561）进行基因分型（聚合酶链反应-限制性片段长度多态性[PCR-RFLP]分析），检测COQ2基因座内的rs6535454和rs4693075多态性。
SAMS患者中rs6535454的分布（GG = 51.1%，GA = 40.0%，AA = 8.9%）与人群对照（GG = 48.1%，GA = 45.0%，AA = 6.9%）或无SAMS的患者（GG = 49.8%，GA = 40.3%，AA = 9.7%）相比，差异无统计学意义（p = 0.33；分析的共显性模型分别为0.32）。同样，rs4693075也与SAMS无关（SAMS患者中CC = 36.8%，CG = 48.2%，GG = 15.0%，对照组中CC = 3并6.6%，CG = 47.5%，GG = 15.9%，无症状患者中CC = 35.8%，CG = 48.2%，GG = 15.9%，分析的共显性模型p = 0.94和0.95）。此外，分析的各组之间单倍型分布也无显著差异。
在接受低剂量他汀类药物治疗的捷克患者中，COQ2基因多态性与SAMS无关。这是辅酶Q10途径对SAMS发生并非最重要的又一证据。
