Genome-Wide Association Study Identifies CDKN1A as a Novel Locus Associated with Muscle Fiber Composition.
Genome-Wide Association Study Identifies CDKN1A as a Novel Locus Associated with Muscle Fiber Composition.
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作者：
肌纤维组成与身体表现相关，耐力运动员与力量运动员相比具有高比例的慢收缩肌纤维。大约45%的肌纤维组成是可遗传的，然而，肌纤维类型个体间差异的单核苷酸多态性（SNP）在很大程度上仍然未知。基于三个全基因组SNP数据集，我们已经表明，位于细胞周期蛋白依赖性激酶抑制剂1A（CDKN 1A）基因附近的rs 236448 A等位基因与俄罗斯人慢收缩肌纤维比例增加相关。（n = 151; p = 0.039）、芬兰（n = 287; p = 0.03）和日本（n = 207; p = 0.008）队列（荟萃分析：p = 7.9 × 10−5）。此外，rs 236448 A等位基因的频率在俄罗斯（p = 0.045）和日本（p = 0.038）优秀耐力运动员中显著高于种族匹配的力量运动员。相反，C等位基因与更大比例的快缩肌纤维和力量运动的倾向有关。CDKN 1A参与细胞周期调控，并被miR-208 b抑制，miR-208 b在慢肌纤维基因程序的激活中起重要作用。生物信息学分析显示，rs 236448 C等位基因与全血中CDKN 1A表达增加（p = 8.5 × 10−15）和更大的无脂肪体重（p = 1.2 × 10−5）相关，而A等位基因与英国生物库队列中报告的更长时间的运动（p = 0.044）相关。此外，CDKN 1A的表达在对力量（p < 0.0001）或短跑（p = 0.00035）训练的反应中增加。因此，我们发现CDKN 1A的表达在乳腺癌中显著（p = 0.002）更高。力量型运动员的股外侧肌与耐力型运动员相比，与快缩肌纤维百分比呈正相关（p = 0.018）。总之，我们的数据表明，CDKN 1A rs 236448 SNP可能与肌纤维组成的测定有关，并可能影响运动表现。
Muscle fiber composition is associated with physical performance, with endurance athletes having a high proportion of slow-twitch muscle fibers compared to power athletes. Approximately 45% of muscle fiber composition is heritable, however, single nucleotide polymorphisms (SNP) underlying inter-individual differences in muscle fiber types remain largely unknown. Based on three whole genome SNP datasets, we have shown that the rs236448 A allele located near the cyclin-dependent kinase inhibitor 1A (CDKN1A) gene was associated with an increased proportion of slow-twitch muscle fibers in Russian (n = 151; p = 0.039), Finnish (n = 287; p = 0.03), and Japanese (n = 207; p = 0.008) cohorts (meta-analysis: p = 7.9 × 10−5. Furthermore, the frequency of the rs236448 A allele was significantly higher in Russian (p = 0.045) and Japanese (p = 0.038) elite endurance athletes compared to ethnically matched power athletes. On the contrary, the C allele was associated with a greater proportion of fast-twitch muscle fibers and a predisposition to power sports. CDKN1A participates in cell cycle regulation and is suppressed by the miR-208b, which has a prominent role in the activation of the slow myofiber gene program. Bioinformatic analysis revealed that the rs236448 C allele was associated with increased CDKN1A expression in whole blood (p = 8.5 × 10−15) and with greater appendicular lean mass (p = 1.2 × 10−5), whereas the A allele was associated with longer durations of exercise (p = 0.044) reported amongst the UK Biobank cohort. Furthermore, the expression of CDKN1A increased in response to strength (p < 0.0001) or sprint (p = 0.00035) training. Accordingly, we found that CDKN1A expression is significantly (p = 0.002) higher in the m. vastus lateralis of strength athletes compared to endurance athletes and is positively correlated with the percentage of fast-twitch muscle fibers (p = 0.018). In conclusion, our data suggest that the CDKN1A rs236448 SNP may be implicated in the determination of muscle fiber composition and may affect athletic performance.
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影响因子：
5.6
作者：
Hall ECR;Lysenko EA;Semenova EA;Borisov OV;Andryushchenko ON;Andryushchenko LB;Vepkhvadze TF;Lednev EM;Zmijewski P;Popov DV;Generozov EV;Ahmetov II
通讯作者：
Ahmetov II
影响因子：
3.5
作者：
Takaragawa M;Tobina T;Shiose K;Kakigi R;Tsuzuki T;Ichinoseki-Sekine N;Kumagai H;Zempo H;Miyamoto-Mikami E;Kobayashi H;Naito H;Fuku N
通讯作者：
Fuku N
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ
DOI：
10.1016/j.bbagen.2021.130048
发表时间：
2022-03
期刊：
Biochimica et biophysica acta. General subjects
影响因子：
--
作者：
Kumagai H;Natsume T;Kim SJ;Tobina T;Miyamoto-Mikami E;Shiose K;Ichinoseki-Sekine N;Kakigi R;Tsuzuki T;Miller B;Yen K;Murakami H;Miyachi M;Zempo H;Dobashi S;Machida S;Kobayashi H;Naito H;Cohen P;Fuku N
通讯作者：
Fuku N
影响因子：
5.6
作者：
Boulygina, Eugenia A.;Borisov, Oleg, V;Ahmetov, Ildus I.
通讯作者：
Ahmetov, Ildus I.