Infect Immun. 2014 Mar 31. [Epub ahead of print]

ALOX12 In Human Toxoplasmosis

Witola WH¹, Liu SR, Montpetit A, Welti R, Hypolite M, Roth M, Zhou Y, Mui E, Cesbron-Delauw MF, Fournie GJ, Cavailles P, Bisanz C, Boyer K, Withers S, Noble AG, Swisher CN, Heydemann PT, Rabiah P, McLeod R.

Abstract

ALOX12 is a gene encoding arachidonate 12-lipoxygenase (12-LOX), a member of a non-heme lipoxygenase family of dioxygenases. ALOX12 catalyzes the addition of oxygen onto arachidonic acid producing 12-hydroperoxyeicosatetraenoic acid, 12-HPETE, which can be reduced to eicosanoid, 12-HETE. 12-HETE acts in diverse cellular processes including catecholamine synthesis, vasoconstriction, neuronal function and inflammation. Consistent with effects on these fundamental mechanisms, allelic variants of ALOX12 are associated with diseases including schizophrenia, atherosclerosis and cancers without definition of mechanisms. Toxoplasma gondii is an apicomplexan parasite that causes morbidity and mortality and stimulates an innate and adaptive immune inflammatory reaction. Recently, it has been shown that a gene region known as Toxo1 is critical for susceptibility or resistance to T. gondii infection in rats. An orthologous gene region with ALOX12 centromeric is also present in humans. Herein, we report that the human ALOX12 gene has susceptibility alleles for human congenital toxoplasmosis (rs6502997 [P<0 .000309="" a="" acid="" alox12.="" alox12="" and="" arachidonic="" attenuated="" be="" been="" burden="" but="" cell="" cells.="" cells="" consequent="" critical="" death="" decreased="" demonstrate="" diseases.="" engineered="" expression="" findings="" genetically="" gondii="" greater="" has="" herein="" host="" human="" humans.="" important="" in="" increased.="" infection="" influences="" interference="" knockdown="" late="" lentivirus="" line.="" line="" monocytic="" now="" numerous="" of="" other="" p="" parasite="" plays="" progression="" responses="" resulted="" rna="" role="" rs312462="" rs434473="" rs6502998="" shown="" studies="" substrate="" suggest="" t.="" that="" the="" these="" to="" using="" was="" we="">

PMID:

24686056

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