Genetic polymorphisms in <i>CYP19A1</i> and <i>ESR1</i> are associated with serum CK activity after prolonged running in men
Genetic polymorphisms in <i>CYP19A1</i> and <i>ESR1</i> are associated with serum CK activity after prolonged running in men
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<i>CYP19A1</i>和<i>ESR1</i>基因多态性与男性长时间跑步后血清CK活性相关
DOI：
10.1152/japplphysiol.00374.2021
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发表时间：
2022
影响因子：
3.3
通讯作者：
Fuku Noriyuki
中科院分区：
文献类型：
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作者：
Kumagai Hiroshi;Miyamoto-Mikami Eri;Takaragawa Mizuki;Kuriki Kiyonori;Goto Chiho;Shibata Kiyoshi;Yamada Norihiro;Hosono Akihiro;Fuku Mizuho;Suzuki Sadao;Fuku Noriyuki
本研究旨在阐明 1) 细胞色素 P450 芳香酶基因 (CYP19A1) 的遗传多态性对男性循环雌二醇水平的影响，以及 2) 雌激素相关的遗传多态性（例如 CYP19A1rs936306 和雌激素受体-α (ESR1) rs2234693 多态性）是否可以预测运动诱发的血清肌酸激酶 (CK)活动，这是骨骼肌膜破坏的指标。对年轻男性 (n = 167) 进行了血清雌二醇水平检查。在另一个队列中，我们在为期 2 天的超级马拉松比赛中分析了血清 CK 活性：基线、第一天后和第二天后（114 名男性和 25 名女性）。使用 TaqMan SNP 基因分型测定分析 CYP19A1rs936306 C/T 和 ESR1rs2234693 T/C 的遗传多态性。具有CYP19A1多态性TT基因型的男性受试者表现出比C等位基因携带者显着更高的血清雌二醇水平。男性跑者赛后血清CK活性显着高于女性跑者。具有 CYP19A1TT 基因型的男性受试者在超级马拉松比赛期间 CK 活性的变化显着低于具有 CC + CT 基因型的男性受试者，并且与男性受试者中 ESR1rs2234693 中的 C 等位基因的数量相关。此外，这两个多态性的基因型评分与比赛期间血清CK活性的变化显着相关（r= –0.279，P= 0.003）。本研究的结果表明，CYP19A1rs936306 的遗传多态性影响男性血清雌二醇水平，CYP19A1 和 ESR1 的遗传多态性与男性血清 CK 活性相关。新与值得注意的 CYP19A1 多态性 TT 基因型的男性比 TC + CC 基因型表现出更高的循环雌二醇水平。 CYP19A1 多态性的 TT 基因型和 ESR1 多态性的 C 等位基因（增加 ESR1 表达的等位基因）与超级马拉松后低血清 CK 活性相关。这些多态性的组合与血清 CK 活性的变化相关。因此，雌激素相关的基因多态性部分预测了运动引起的肌肉损伤，即骨骼肌膜破坏。
This study aimed to clarify1) the influence of genetic polymorphisms in the cytochrome P450 aromatase gene (CYP19A1) on circulating estradiol levels in men and2) whether estrogen-related genetic polymorphisms, such as theCYP19A1rs936306 and estrogen receptor-α (ESR1) rs2234693 polymorphisms, predict exercise-induced serum creatine kinase (CK) activity, which is an index of skeletal muscle membrane disruption. Serum estradiol levels were examined in young men (n= 167). In a different cohort, serum CK activity was analyzed in a 2-day ultramarathon race: baseline, after the first day, and after the second day (114 males and 25 females). Genetic polymorphisms inCYP19A1rs936306 C/T andESR1rs2234693 T/C were analyzed using the TaqMan SNP Genotyping Assay. Male subjects with the TT genotype of theCYP19A1polymorphism exhibited significantly higher serum estradiol levels than the C allele carriers. Male runners had significantly higher postrace serum CK activity than female runners. The change in the CK activity during the ultramarathon race was significantly lower in male subjects with theCYP19A1TT genotype than in those with the CC + CT genotypes and was correlated with the number of C alleles inESR1rs2234693 in male subjects. Furthermore, the genotype scores of these two polymorphisms were significantly correlated with changes in serum CK activity during race (r= –0.279,P= 0.003). The results of this study suggest that genetic polymorphisms inCYP19A1rs936306 influence serum estradiol levels in men, and genetic polymorphisms inCYP19A1andESR1are associated with serum CK activity in men.NEW & NOTEWORTHYMen with the TT genotype of theCYP19A1polymorphism exhibited higher circulating estradiol levels than the TC + CC genotype. The TT genotype in theCYP19A1polymorphism and the C allele of theESR1polymorphism, an allele increasingESR1expression, were associated with low serum CK activity after the ultramarathon. A combination of these polymorphisms was correlated with changes in the serum CK activity. Therefore, estrogen-related genetic polymorphisms partially predict exercise-induced muscle damage, that is, skeletal muscle membrane disruption.