Yale School of Medicine, Department of Medicine, New Haven, CT, United States of America; Veterans Affairs Connecticut Healthcare System, Department of Medicine, West Haven, CT, United States of America.
University of Florida, Department of Aging and Geriatric Research, Gainesville, FL, United States of America.
Exp Gerontol. 2019 Jan;115:96-103. doi: 10.1016/j.exger.2018.11.023. Epub 2018 Dec 1.
We provide the first examination of mitochondrial DNA (mtDNA) variants and pulmonary function in older persons.
Cross-sectional associations between mtDNA variants and pulmonary function were evaluated as a combined p-values meta-analysis, using data from two independent cohorts of older persons. The latter included white and black participants, aged ≥70 years, from the Lifestyle Interventions and Independence for Elders study (LIFE) (N = 1247) and the Health, Aging and Body Composition study (Health ABC) (N = 731), respectively. Pulmonary function included the forced expiratory volume in one-second as a Z-score (FEV1z) and the maximal inspiratory pressure (MIP) in cm of water.
In black participants, significant associations were found between mtDNA variants and MIP: m.7146A > G, COI (p = 3E-5); m.7389 T > C, COI (p = 2E-4); m.15301G > A, CYB (p = 9E-5); m.16265A > G, HV1 (p = 9E-5); meta-analytical p-values <0.0002. Importantly, these mtDNA variants were unique to black participants and were not present in white participants. Moreover, in black participants, aggregate genetic effects on MIP were observed across mutations in oxidative phosphorylation complex IV (p = 0.004), complex V (p = 0.0007), and hypervariable (p = 0.003) regions. The individual and aggregate variant results were significant after adjustment for multiple comparisons. Otherwise, no significant associations were detected for MIP in whites or for FEV1z in whites or blacks.
We have shown that mtDNA variants of African origin are cross-sectionally associated with MIP, a measure of respiratory muscle strength. Thus, our results establish the rationale for longitudinal studies to evaluate whether mtDNA variants of African origin identify those at risk of subsequently developing a respiratory muscle impairment (lower MIP values).
我们首次研究了线粒体 DNA（mtDNA）变异与老年人肺功能之间的关系。
采用合并的 p 值荟萃分析方法，评估 mtDNA 变异与肺功能之间的横断面关联，该分析使用了来自两个独立的老年人队列的数据。后者包括来自生活方式干预和老年人独立研究（LIFE）（N=1247）的白人和黑人参与者，年龄≥70 岁，以及来自健康、老龄化和身体成分研究（Health ABC）（N=731）的参与者。肺功能包括 1 秒用力呼气量的 Z 分数（FEV1z）和最大吸气压力（MIP）以厘米水柱表示。
在黑人参与者中，发现 mtDNA 变异与 MIP 之间存在显著关联：COI 上 m.7146A>G（p=3E-5）；COI 上 m.7389T>C（p=2E-4）；CYB 上 m.15301G>A（p=9E-5）；HV1 上 m.16265A>G（p=9E-5）；荟萃分析 p 值<0.0002。重要的是，这些 mtDNA 变异仅存在于黑人参与者中，而不存在于白人参与者中。此外，在黑人参与者中，观察到氧化磷酸化复合物 IV（p=0.004）、复合物 V（p=0.0007）和高变区（p=0.003）突变的 MIP 整体遗传效应。个体和聚集变异结果在经过多次比较调整后仍然显著。否则，在白人或黑人群体中，均未检测到 MIP 与 FEV1z 之间存在显著关联。
我们已经表明，起源于非洲的 mtDNA 变异与 MIP （呼吸肌力量的衡量指标）呈横断面相关。因此，我们的研究结果为评估起源于非洲的 mtDNA 变异是否能识别随后发生呼吸肌损伤（较低的 MIP 值）风险的纵向研究提供了依据。
