76 2018 58 6 Journal of Nanchang University Medical Sciences 2018 Vol.58 No.6 G6P 650500-6- glucose-6-phosphate dehydrogenase G6P Xq28 G6P G6P Ⅱ NPH GSH G6P G6P G6P G6P G6P G6P -6- R556.6 OI 10.13764 /j.cnki.ncdm.2018.06.018 2095-4727 2018 06-0076-05 Research dvances in Selection dvantage and Resistance Mechanism of G6P eficiency and Malaria YI Hao-an H Yong-shu epartment of ell iology and Medical Genetics Kunming Medical University Kunming 650500 hina STRT The glucose-6-phosphate dehydrogenase G6P deficiency is a common hereditary hemolytic disease.g6p gene is located at Xq28.G6P gene mutation induces the decrease in G6P activity and red blood cell NPH and GSH levels resulting in oxidative cell damage and hemolytic reaction.malaria is a serious insect-borne disease endangering human health.malaria-endemic areasare consistent with the high prevalence regions of G6P deficiency. It is widely believed that G6P deficiency has a resistance to malaria under the selective pressure of malaria.however the resistance mechanism is unclear.this article reviews the progress in mechanism of G6P deficiency against malaria to further explore the complicated relationship between G6P deficiency and malaria. KY WORS glucose-6-phosphate dehydrogenase deficiency malaria selection advantage resistance mechanism -6- glucose-6-phosphate dehydrogenase G6P G6P G6P G6P Xq2813 12 1 4 20 114 bp 515 2018-04-02 31760308 31260264 1995 -mail yongshuhe@ hotmail.com
G6P 77 2 G6P Ⅱ NPH GSH G6P G6P 31 G6P 1376G>T 1388G> 95>G 70% WHO G6P G6P Ⅱ Ⅲ G6P 7 1.2 5% 100 8 4 9 uffy O 34 G6P α- β- HbS Hb Hb 3 G6P G6P G6P 4 G6P G6P 10-11 1 G6P 1.3 G6P 1.1 G6P 1.3.1 G6P G6P G6P G6P X 12 G6P G6P 13 G6P NPH NPH GSH 5 G6P NPH G6P GSH 6 GSH G6P G6P 3 1 186 G6P G6P
78 2018 12 58 6 G6P G6P 24 G6P 14 G6P G6P G6P 15 2 G6P 1.3.2 G6P G6P G6P G6P G6P G6P Santana 16 G6P G6P- 376>G /202 G> G6P G6P Louicharoen 14 G6P Mahidol 487G> 25 2500~3800 G6P G6P G6P Li 17 G6P Mahidol 487G> 26 ROS 27 G6P G6P NPH G6P GSH 28 18-19 G6P G6P V X 20 G6P 29 G6P G6P G6P 21 Heinzbody 30 G6P 31 G6P 22 T 32 23 G6P G6P a 2+ a 2+ 33 G6P G6P 16 G6P 34 G6P
G6P 79 35 iol hem 2011 35 3 189-192. 8 harati K GSH GSSG 8-10 GSSG NPH J 2017 NP NPH 655. 36 12 Wilson M L Krogstad J rinaitwe seven diverse IMR network sites J 37 2015 93 3 Suppl 110-123. 13 Howes R attle K Satyagraha W G6P global distribution dv Parasitol 2013 81 133-201. 3 G6P G6P 15 Manganelli G Masullo U Passarelli S J.ardiovasc Hematol isord rug Targets G6P 82. 16 Santana M S Monteiro W M Siqueira M G6P susceptibility to malaria in the razilian mazon J Trop Med Hyg 2013 107 5 301-306. 17 Li Q Yang F Liu R 1 appellini M Fiorelli G.Glucose-6-phosphate dehydrogenase deficiency J.Lancet 2008 371 9606 64-74. 19.G6P 2.G-6-P J. J. 2014 30 21 3418-3421. 2001 23 3 466-467. 3 Gomez F Ko W Y avis et al.impact of natural selection due to malarial disease on human genetic variation M / /rinkworth J F Pechenkina K.Primates Pathogens and volution.new York NY Springer New York 2013 117-160. 4 Sirugo G.Reassessing an old claim natural selection of hemizygotes and heterozygotes for G6P deficiency in frica by resistance to severe malaria J.m J Hematol 2013 88 5 436. 5 Yang H Wu Y H Liu H Y et al.what has passed is prolog new cellular and physiological roles of G6P J. Free Radic Res 2016 50 10 1047-1064. 6 Gomez Manzo S Marcial Quino J Vanoye arlo et al.glucose-6- Phosphate dehydrogenase update and analysis of new mutations a- round the world J.Int J Mol Sci 2016 17 12.Pii 2069. 7 Yang Y Li Z Nan P et al.rug-induced glucose-6-phosphate dehydrogenase deficiency-related hemolysis risk assessment J.omput Ganguly N K.Tackling the malaria problem in the southeast asia region need for a change in policy J.Indian J Med Res 2013 137 1 36-47. 9 Mconald R Tran V Kain K. omplement activation in placental malaria J.Front Microbiol 2015 6 1460.. J. 2013 25 1 36-39. 11.. 29 5 651- et al.urban malaria understanding its epidemiology ecology and transmission across. m J Trop Med Hyg et al.g6p deficiency genetic variants and primaquine therapy J. 14 Louicharoen Patin Paul R et al. Positively selected G6P- Mahidol mutation reduces plasmodium vivax density in southeast asians J.Science 2009 326 5959 1546-1549. et al.glucose-6-phosphate dehydrogenase deficiency disadvantages and possible benefits 2013 13 1 73- et al.glucose-6-phosphate dehydrogenase deficient variants are associated with reduced.trans R Soc et al.prevalence and molecular characterization of glucose-6-phosphate dehydrogenase deficiency at the china-myanmar border J.PLoS One 2015 10 7 e0134593. 18 Guindo Fairhurst R M oumbo O K et al.x-linked G6P deficiency protects hemizygous males but not heterozygous females against severe malaria J.PLoS Med 2007 4 3 e66. 20 Wang J Xiao Q Z hen Y M et al.n hypermethylation and X chromosome inactivation are major determinants of phenotypic variation in women heterozygous for G6P mutations J. lood ells Mol is 2014 53 4 241-245. 21 hen X He Y Miao Y et al. young man with severe acute haemolytic anaemia J.MJ 2017 359 j4263. 22 Lalloo G Shingadia ell J et al. UK malaria treatment guidelines 2016 J.J Infect 2016 72 6 635-649. 23 Gyr K Speck Ritz R et al. erebral tropical malaria with blackwater fever. current diagnostic and therapeutic problem J.Schweiz Med Wochenschr 1974 104 45 1628-1630. 24 Luzzatto L Seneca.G6P deficiency a classic example of pharmacogenetics with on-going clinical implications J.r J Haematol 2014 164 4 469-480. 25 ilgin R Yalcin M S Yucebilgic G et al.oxidative stress in vivax malaria J.Korean J Parasitol 2012 50 4 375-377.
80 2018 12 58 6 26 Foth J Zhang N haal K et al.quantitative time-course profiling of parasite and host cell proteins in the human malaria parasite Plasmodium falciparum J. Mol ell Proteomics 2011 10 8 M110.006411. 27 Toler S.The plasmodial apicoplast was retained under evolutionary selective pressure to assuage blood stage oxidative stress J.Med Hypotheses 2005 65 4 683-690. 28 Tang H Y Ho H Y Wu P R et al.inability to maintain GSH pool in G6P-deficient red cells causes futile MPK activation and irreversible metabolic disturbance J. ntioxid Redox Signal 2015 22 9 744-759. 29 Klonis N Tan O Jackson K et al.valuation of ph during cytostomal endocytosis and vacuolar catabolism of haemoglobin in Plasmodium falciparum J.iochem J 2007 407 3 343-354. 30 Ronquist G Theodorsson.Inherited non-spherocytic haemolysis due to deficiency of glucose-6-phosphate dehydrogenase J. Scand J lin Lab Invest 2007 67 1 105-111. 31 dachi H.Pathological study on experimental Heinz body anemia intracellular changes of phagocytized red cells in macrophages of the spleen and liver J.cta Pathol Jpn 1977 27 5 657-675. 32 Wu J Tian L Yu X et al.strain-specific innate immune signaling pathways determine malaria parasitemia dynamics and host mortality J.Proc Natl cad Sci U S 2014 111 4 511-520. 33 Foller M Huber S M Lang F.rythrocyte programmed cell death J.IUM Life 2008 60 10 661-668. 34 Fang Z Jiang Tang J et al. comprehensive analysis of membrane and morphology of erythrocytes from patients with glucose- 6-phosphate dehydrogenase deficiency J. J Struct iol 2016 194 3 235-243. 35 uez J Holleran J P Ndour P et al. Mechanical clearance of red blood cells by the human spleen Potential therapeutic applications of a biomimetic R filtration method J. Transfus lin iol 2015 22 3 151-157. 36 Thornalley P J Stern annister J V. mechanism for primaquine mediated oxidation of NPH in red blood cells J.iochem Pharmacol 1983 32 23 3571-3575. 37 Zyad Tilaoui M.More insights into the pharmacological effects of artemisinin J.2018 32 2 216-229. 櫐櫐櫐櫐櫐櫐櫐櫐櫐櫐櫐櫐櫐櫐櫐櫐櫐櫐櫐櫐櫐櫐櫐櫐櫐櫐櫐櫐櫐櫐櫐櫐櫐櫐櫐櫐櫐櫐櫐櫐櫐櫐櫐櫐櫐櫐 75 5.2013-2014 HIV rapid test among men who have sex with men in eijing hina J. 2015 26 5 379-382. 6. 1324 HIV HV HV J. 2012 28 7 854-855. 7. 372 HV 16. HIV J. 2014 24 19 J. 2016 28 2860-2861. 8. 17.2010 J. 2013 24 4 HIV HV J. 24-25. 9. HIV HV HV 18. HIV HV HV J. J. 2014 28 7 480-481. 2011 26 1 62-64. 10. 2013. J. 2010 26 11 1263-1264. 11. 2010 14 4 300-304. J. 21. HIV HV 2015 41 5 44-48. J. 2091 41 12. HIV 11 2079-2081 2091. J. 2011 27 1 104-105. 13. J. J 2016 25 7 2009 15 5 19-21. 1157-1160. 14 Xu Y Zhang Z Li et al.willingness to use the oral fluid HIV J.PLoS One 2013 8 5 e64652. 15 Pai N P arick R Tulsky J P et al.impact of round-the-clock rapid oral fluid HIV testing of women in labor in rural India J.PLOS Med 2008 5 5 e92. 5 315-317. 2012 18 1 31-33. 19. 20. HIV HV HV Meta J. 22. HIV HV
依达拉奉联合参麦注射液对窒息新生大鼠的心肌保护作用 正文见第 20 页 组 组 组 组 组 图1 各组心肌组织病理改变 H 染色 200 组 组 组 组 组 图2 各组心肌组织 p-p38mpk 蛋白表达 免疫组化 400 组 组 组 组 组 图3 各组心肌组织 cl-2 蛋白表达 免疫组化 400 组 组 组 组 组 图4 各组心肌细胞凋亡荧光显色 Tunel 法 400 G6P 缺乏症与疟疾的选择优势及抗性机制研究进展 正文见第 76 页 G6P 缺乏症分布图 疟疾分布图 图1 我国南方及东南亚周边国家 G6P 缺乏症 疟疾分布图