Genomic predictors of the maximal O2 uptake response to standardized exercise training programs
Genomic predictors of the maximal O2 uptake response to standardized exercise training programs
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DOI：
10.1152/japplphysiol.00973.2010
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发表时间：
2011-05-01
影响因子：
3.3
通讯作者：
Rankinen, Tuomo
中科院分区：
文献类型：
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作者：
Bouchard, Claude;Sarzynski, Mark A.;Rankinen, Tuomo
低心肺适应性是发病率和心血管死亡率的有力预测因子。在健康、危险因素、运动训练和遗传学（HERITAGE）家庭研究的99个家庭中，473名久坐不动的成年人（均为白人）中，暴露于标准化的20周运动计划后，最大O-2摄取（O-2 max）增益的遗传率估计为47%。进行了一项基于324，611个单核苷酸多态性（SNP）的全基因组关联研究，以确定与O-2 max改善相关的SNP。基于单SNP分析，39个SNP与P < 1.5 < 10（-4）的增益相关。39个SNP的逐步多元回归分析确定了一组21个SNP，占O-2 max可训练性方差的49%。携带≥ 19个等位基因的受试者平均增加604 ml/min。最强的关联是位于酰基辅酶A合成酶长链成员1（ACSL 1）基因中的rs6552828，其本身占O-2 max训练反应的6%。最接近SNPs的基因是具有ZNF结构域的PR结构域1（PRDM 1）;谷氨酸受体，离子型，N-甲基-D-天冬氨酸3A（GRIN 3A）; K+通道，电压门控，H亚家族，成员8（KCNH 8）;和小脑锌指蛋白4（ZIC 4）。与最接近ZIC 4的SNP的关联在40- 65岁、久坐、超重和血脂异常的受试者中得到复制，这些受试者接受了通过规定运动进行有针对性的风险降低干预研究（STRRIDE; n = 183）的培训。在运动剂量反应（DREW）研究中（n = 112），在久坐不动的肥胖白色女性运动训练中复制了两个SNP：rs 1956197靠近形态发生相关激活因子1（DAAM 1），rs 17117533靠近necdin（NDN）。钙调蛋白结合转录激活因子1（CAMTA 1）基因座中的SNP rs 884736和G蛋白信号转导调节因子18（RGS 18）上游68 kb处相似的rs 17581162与HERITAGE白人O-2 max增加的相关性在HERITAGE黑人中得到了复制（n = 247）。这些基因组预测O-2 max对定期运动的反应，为健身生物学及其对定期运动的适应性研究提供了新的靶点。大规模的复制研究是必要的。
Low cardiorespiratory fitness is a powerful predictor of morbidity and cardiovascular mortality. In 473 sedentary adults, all whites, from 99 families of the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family Study, the heritability of gains in maximal O-2 uptake (O-2max) after exposure to a standardized 20-wk exercise program was estimated at 47%. A genome-wide association study based on 324,611 single-nucleotide polymorphisms (SNPs) was undertaken to identify SNPs associated with improvements in O-2max Based on single-SNP analysis, 39 SNPs were associated with the gains with P < 1.5 < 10(-4). Stepwise multiple regression analysis of the 39 SNPs identified a panel of 21 SNPs that accounted for 49% of the variance in O-2max trainability. Subjects who carried = 19 of these alleles gained, on average, 604 ml/min. The strongest association was with rs6552828, located in the acyl-CoA synthase long-chain member 1 (ACSL1) gene, which accounted by itself for similar to 6% of the training response of O-2max. The genes nearest to the SNPs that were the strongest predictors were PR domain-containing 1 with ZNF domain (PRDM1); glutamate receptor, ionotropic, N-methyl-D-aspartate 3A (GRIN3A); K+ channel, voltage gated, subfamily H, member 8 (KCNH8); and zinc finger protein of the cerebellum 4 (ZIC4). The association with the SNP nearest to ZIC4 was replicated in 40- to 65-yr-old, sedentary, overweight, and dyslipidemic subjects trained in Studies of a Targeted Risk Reduction Intervention Through Defined Exercise (STRRIDE; n = 183). Two SNPs were replicated in sedentary obese white women exercise trained in the Dose Response to Exercise (DREW) study (n = 112): rs1956197 near dishevelled associated activator of morphogenesis 1 (DAAM1) and rs17117533 in the vicinity of necdin (NDN). The association of SNPs rs884736 in the calmodulin-binding transcription activator 1 (CAMTA1) locus and rs17581162 similar to 68 kb upstream from regulator of G protein signaling 18 (RGS18) with the gains in O-2max in HERITAGE whites were replicated in HERITAGE blacks (n = 247). These genomic predictors of the response of O-2max to regular exercise provide new targets for the study of the biology of fitness and its adaptation to regular exercise. Large-scale replication studies are warranted.