ALOX12 in human toxoplasmosis.

[congenital toxoplasmosis]

ALOX 12 is a gene encoding arachidonate 12 -lipoxygenase (12 -LOX ), a member of a nonheme lipoxygenase family of dioxygenases . ALOX 12 catalyzes the addition of oxygen to arachidonic acid , producing 12 -hydroperoxyeicosatetraenoic acid (12 -HPETE ), which can be reduced to the eicosanoid 12 -HETE (12 -hydroxyeicosatetraenoic acid ). 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 ALOX 12 are associated with diseases including schizophrenia , atherosclerosis , and cancers , but the mechanisms have not been defined . 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 Toxo 1 is critical for susceptibility or resistance to T . gondii infection in rats . An orthologous gene region with ALOX 12 centromeric is also present in humans . Here we report that the human ALOX 12 gene has susceptibility alleles for human congenital toxoplasmosis (rs 6502997 [P , <0 .000309 ], rs 312462 [P , <0 .028499 ], rs 6502998 [P , <0 .029794 ], and rs 434473 [P , <0 .038516 ]). A human monocytic cell line was genetically engineered using lentivirus RNA interference to knock down ALOX 12 . In ALOX 12 knockdown cells , ALOX 12 RNA expression decreased and levels of the ALOX 12 substrate , arachidonic acid , increased . ALOX 12 knockdown attenuated the progression of T . gondii infection and resulted in greater parasite burdens but decreased consequent late cell death of the human monocytic cell line . These findings suggest that ALOX 12 influences host responses to T . gondii infection in human cells . ALOX 12 has been shown in other studies to be important in numerous diseases . Here we demonstrate the critical role ALOX 12 plays in T . gondii infection in humans .

Diseases
Validation

Diseases presenting "susceptibility alleles" symptom

congenital toxoplasmosis

hydrocephalus with stenosis of the aqueduct of sylvius

oligodontia

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