Research Center for Exercise and Health, Department of Biomedical Kinesiology, Faculty of Kinesiology and Rehabilitation Sciences, Katholieke Universiteit Leuven, Leuven, Belgium.
Physiol Genomics. 2011 Sep 8;43(17):981-92. doi: 10.1152/physiolgenomics.00200.2010. Epub 2011 Jul 12.
Muscle strength is an important determinant in elite sports performance as well as in the activities of daily living. Muscle metabolism also plays a role in the genesis, and therefore prevention, of common pathological conditions and chronic diseases. Even though heritability estimates between 31 and 78% suggest a significant genetic component in muscle strength, only a limited number of genes influencing muscle strength have been identified. This study aimed to identify and prioritize positional candidate genes within a skeletal muscle strength quantitative trait locus on chromosome 12q22-23 for follow-up. A two-staged gene-centered fine-mapping approach using 122 single nucleotide polymorphisms (SNPs) in stage 1 identified a family-based association (n=500) between several tagSNPs located in the ATPase, Ca2+ transporting, cardiac muscle, slow twitch 2 (ATP2A2; rs3026468), the NUAK family, SNF1-like kinase, 1 (NUAK1; rs10861553 and rs3741886), and the protein phosphatase 1, catalytic subunit, gamma isoform (PPP1CC; rs1050587 and rs7901769) genes and knee torque production (P values up to 0.00092). In stage 2, family-based association tests on additional putatively functional SNPs (e.g., exonic SNPs, SNPs in transcription factor binding sites or in conserved regions) in an enlarged sample (n=536; 464 individuals overlap with stage 1) did not identify additional associations with muscle strength characteristics. Further in-depth analyses will be necessary to elucidate the exact role of ATP2A2, PPP1CC, and NUAK1 in muscle strength and to find out which functional polymorphisms are at the base of the interindividual strength differences.
肌肉力量是精英运动表现以及日常生活活动的重要决定因素。肌肉代谢在常见病理状况和慢性疾病的发生中也起着作用。尽管遗传率估计在 31%至 78%之间表明肌肉力量具有重要的遗传成分，但只有少数基因能够影响肌肉力量。本研究旨在鉴定和优先考虑位于染色体 12q22-23 上的骨骼肌力量数量性状基因座内的位置候选基因，以便进一步研究。使用阶段 1 中的 122 个单核苷酸多态性（SNP）进行的两阶段基于基因的精细映射方法确定了几个位于 ATP 酶、Ca2+转运、心肌、慢收缩 2（ATP2A2；rs3026468）、NUAK 家族、SNF1 样激酶、1（NUAK1；rs10861553 和 rs3741886）和蛋白磷酸酶 1、催化亚基、γ 同工型（PPP1CC；rs1050587 和 rs7901769）基因与膝关节扭矩产生之间的基于家庭的关联（n=500）（P 值高达 0.00092）。在第二阶段，在更大的样本（n=536；464 个人与阶段 1 重叠）中对其他推定功能 SNP（例如外显子 SNP、转录因子结合位点或保守区域中的 SNP）进行基于家庭的关联测试，未鉴定出与肌肉力量特征相关的其他关联。需要进一步深入分析，以阐明 ATP2A2、PPP1CC 和 NUAK1 在肌肉力量中的确切作用，并找出导致个体间力量差异的基础的功能多态性。
