The potential link between inherited G6PD deficiency, oxidative stress, and vitamin D deficiency and the racial inequities in mortality associated with COVID-19.
The potential link between inherited G6PD deficiency, oxidative stress, and vitamin D deficiency and the racial inequities in mortality associated with COVID-19.
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DOI：
10.1016/j.freeradbiomed.2020.10.002
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发表时间：
2020-12
影响因子：
7.4
通讯作者：
Vanchiere JA
中科院分区：
文献类型：
--
作者：
Jain SK;Parsanathan R;Levine SN;Bocchini JA;Holick MF;Vanchiere JA
在一般人群中，与COVID-19感染相关的死亡风险存在显著差异。较低的社会经济地位和其他社会决定因素被认为是非洲裔美国人社区比白色社区负担更高的可能原因。除了社会决定因素外，尚不清楚使个体受试者或社区易于发生与COVID-19感染相关的过度和严重并发症的生化机制。病毒感染引发大量ROS产生和氧化损伤。谷胱甘肽（GSH）是必不可少的，保护身体免受过量活性氧自由基氧化损伤的有害影响。GSH还需要维持VD代谢基因和25-羟基维生素D（25（OH）VD）的循环水平。葡萄糖-6-磷酸脱氢酶（G6 PD）是防止细胞GSH耗尽和耗竭所必需的。X连锁遗传性G6 PD缺乏症在AA人群中很常见，主要发生在男性中。在患有肥胖症和糖尿病的受试者中已经广泛报道了获得性G6 PD缺乏症。这表明G6 PD缺乏症患者容易受到过度氧化应激的影响，并且25（OH）VD不足或缺乏的风险更高，使身体无法保护其“氧化免疫代谢”生理功能免受COVID-19的伤害。亚临床间质性肺病与25（OH）VD缺乏和GSH缺乏之间的相关性先前已有报道。我们假设，ROS的过度产生和过度氧化损伤是导致免疫受损、细胞因子风暴分泌和COVID-19感染后肺功能障碍发作的原因。受损的谷胱甘肽氧化还原状态和过量的25（OH）VD缺乏的共同优化有可能减少氧化应激，增强免疫力，并减少AA人群中COVID-19感染的不良临床影响。
There is a marked variation in mortality risk associated with COVID-19 infection in the general population. Low socioeconomic status and other social determinants have been discussed as possible causes for the higher burden in African American communities compared with white communities. Beyond the social determinants, the biochemical mechanism that predisposes individual subjects or communities to the development of excess and serious complications associated with COVID-19 infection is not clear. Virus infection triggers massive ROS production and oxidative damage. Glutathione (GSH) is essential and protects the body from the harmful effects of oxidative damage from excess reactive oxygen radicals. GSH is also required to maintain the VD-metabolism genes and circulating levels of 25-hydroxyvitamin D (25(OH)VD). Glucose-6-phosphate dehydrogenase (G6PD) is necessary to prevent the exhaustion and depletion of cellular GSH. X-linked genetic G6PD deficiency is common in the AA population and predominantly in males. Acquired deficiency of G6PD has been widely reported in subjects with conditions of obesity and diabetes. This suggests that individuals with G6PD deficiency are vulnerable to excess oxidative stress and at a higher risk for inadequacy or deficiency of 25(OH)VD, leaving the body unable to protect its ‘oxidative immune-metabolic’ physiological functions from the insults of COVID-19. An association between subclinical interstitial lung disease with 25(OH)VD deficiencies and GSH deficiencies has been previously reported. We hypothesize that the overproduction of ROS and excess oxidative damage is responsible for the impaired immunity, secretion of the cytokine storm, and onset of pulmonary dysfunction in response to the COVID-19 infection. The co-optimization of impaired glutathione redox status and excess 25(OH)VD deficiencies has the potential to reduce oxidative stress, boost immunity, and reduce the adverse clinical effects of COVID-19 infection in the AA population.
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DOI：
10.15585/mmwr.mm6915e3
发表时间：
2020-04-17
期刊：
MMWR. Morbidity and mortality weekly report
影响因子：
--
作者：
Garg S;Kim L;Whitaker M;O'Halloran A;Cummings C;Holstein R;Prill M;Chai SJ;Kirley PD;Alden NB;Kawasaki B;Yousey-Hindes K;Niccolai L;Anderson EJ;Openo KP;Weigel A;Monroe ML;Ryan P;Henderson J;Kim S;Como-Sabetti K;Lynfield R;Sosin D;Torres S;Muse A;Bennett NM;Billing L;Sutton M;West N;Schaffner W;Talbot HK;Aquino C;George A;Budd A;Brammer L;Langley G;Hall AJ;Fry A
通讯作者：
Fry A
影响因子：
10.6
作者：
Forman, Henry Jay;Zhang, Hongqiao;Rinna, Alessandra
通讯作者：
Rinna, Alessandra
影响因子：
7.7
作者：
Darmaun, D;Smith, SD;Mauras, N
通讯作者：
Mauras, N
影响因子：
3.7
作者：
Farhangi, Mandieh Abbasalizad;Najafi, Mandi
通讯作者：
Najafi, Mandi
DOI：
10.1152/ajpheart.00784.2014
发表时间：
2015-03-01
影响因子：
4.8
作者：
Deo, Shekhar H.;Holwerda, Seth W.;Fadel, Paul J.
通讯作者：
Fadel, Paul J.