Association of ADAMTS13 polymorphism with cerebral malaria
<p>Abstract</p> <p>Background</p> <p>Cerebral malaria is one of the most severe manifestations of <it>Plasmodium falciparum </it>malaria. The sequestration of parasitized red blood cells (PRBCs) to brain microvascular endothelium has been shown to contribute...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2011-12-01
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| Series: | Malaria Journal |
| Online Access: | http://www.malariajournal.com/content/10/1/366 |
| _version_ | 1818806304646365184 |
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| author | Kraisin Sirima Naka Izumi Patarapotikul Jintana Nantakomol Duangdao Nuchnoi Pornlada Hananantachai Hathairad Tsuchiya Naoyuki Ohashi Jun |
| author_facet | Kraisin Sirima Naka Izumi Patarapotikul Jintana Nantakomol Duangdao Nuchnoi Pornlada Hananantachai Hathairad Tsuchiya Naoyuki Ohashi Jun |
| author_sort | Kraisin Sirima |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Cerebral malaria is one of the most severe manifestations of <it>Plasmodium falciparum </it>malaria. The sequestration of parasitized red blood cells (PRBCs) to brain microvascular endothelium has been shown to contribute to the pathophysiology of cerebral malaria. Recent studies reported increased levels of von Willebrand factor (VWF) and reduced activity of VWF-cleaving protease, ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), in patients with cerebral malaria.</p> <p>Methods</p> <p>Association of six single nucleotide polymorphisms (SNPs) of the <it>ADAMTS13 </it>gene with cerebral malaria was examined in 708 Thai patients with <it>P. falciparum </it>malaria.</p> <p>Results</p> <p>Among six SNPs, the derived allele of a SNP located in intron 28, rs4962153-A, was significantly associated with protection against cerebral malaria when 115 cerebral malaria patients were compared with 367 mild malaria patients (Fisher's exact <it>P</it>-value = 0.0057; OR = 0.27; 95% CI = 0.096-0.76). Significant association was also detected between 115 cerebral malaria and 593 non-cerebral malaria (226 non-cerebral severe malaria and 367 mild malaria) patients (Fisher's exact <it>P</it>-value = 0.012; OR = 0.30; 95% CI = 0.11-0.83).</p> <p>Conclusions</p> <p>Excessive adhesion of PRBCs to the platelet-decorated ultra-large VWF (ULVWF) appears to enhance the sequestration of PRBCs to cerebral microvascular endothelium. The genetic association observed in the present study implies that the regulation of platelet-decorated ULVWF strings by ADAMTS13 may play a role in the development of cerebral malaria.</p> |
| first_indexed | 2024-12-18T19:07:39Z |
| format | Article |
| id | doaj.art-0a4586cdc8d44df691bf4cb88168e479 |
| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-12-18T19:07:39Z |
| publishDate | 2011-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Malaria Journal |
| spelling | doaj.art-0a4586cdc8d44df691bf4cb88168e4792022-12-21T20:56:22ZengBMCMalaria Journal1475-28752011-12-0110136610.1186/1475-2875-10-366Association of ADAMTS13 polymorphism with cerebral malariaKraisin SirimaNaka IzumiPatarapotikul JintanaNantakomol DuangdaoNuchnoi PornladaHananantachai HathairadTsuchiya NaoyukiOhashi Jun<p>Abstract</p> <p>Background</p> <p>Cerebral malaria is one of the most severe manifestations of <it>Plasmodium falciparum </it>malaria. The sequestration of parasitized red blood cells (PRBCs) to brain microvascular endothelium has been shown to contribute to the pathophysiology of cerebral malaria. Recent studies reported increased levels of von Willebrand factor (VWF) and reduced activity of VWF-cleaving protease, ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), in patients with cerebral malaria.</p> <p>Methods</p> <p>Association of six single nucleotide polymorphisms (SNPs) of the <it>ADAMTS13 </it>gene with cerebral malaria was examined in 708 Thai patients with <it>P. falciparum </it>malaria.</p> <p>Results</p> <p>Among six SNPs, the derived allele of a SNP located in intron 28, rs4962153-A, was significantly associated with protection against cerebral malaria when 115 cerebral malaria patients were compared with 367 mild malaria patients (Fisher's exact <it>P</it>-value = 0.0057; OR = 0.27; 95% CI = 0.096-0.76). Significant association was also detected between 115 cerebral malaria and 593 non-cerebral malaria (226 non-cerebral severe malaria and 367 mild malaria) patients (Fisher's exact <it>P</it>-value = 0.012; OR = 0.30; 95% CI = 0.11-0.83).</p> <p>Conclusions</p> <p>Excessive adhesion of PRBCs to the platelet-decorated ultra-large VWF (ULVWF) appears to enhance the sequestration of PRBCs to cerebral microvascular endothelium. The genetic association observed in the present study implies that the regulation of platelet-decorated ULVWF strings by ADAMTS13 may play a role in the development of cerebral malaria.</p>http://www.malariajournal.com/content/10/1/366 |
| spellingShingle | Kraisin Sirima Naka Izumi Patarapotikul Jintana Nantakomol Duangdao Nuchnoi Pornlada Hananantachai Hathairad Tsuchiya Naoyuki Ohashi Jun Association of ADAMTS13 polymorphism with cerebral malaria Malaria Journal |
| title | Association of ADAMTS13 polymorphism with cerebral malaria |
| title_full | Association of ADAMTS13 polymorphism with cerebral malaria |
| title_fullStr | Association of ADAMTS13 polymorphism with cerebral malaria |
| title_full_unstemmed | Association of ADAMTS13 polymorphism with cerebral malaria |
| title_short | Association of ADAMTS13 polymorphism with cerebral malaria |
| title_sort | association of adamts13 polymorphism with cerebral malaria |
| url | http://www.malariajournal.com/content/10/1/366 |
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