Polymorphism in the catalytic subunit of the PI3Kγ gene is associated with Trypanosoma cruzi-induced chronic chagasic cardiomyopathy

被引:2
作者
Silva, Maria Claudia [1 ]
Medina, Tiago da Silva [1 ,2 ]
Fuzo, Carlos Alessandro [3 ]
Dias, Fabricio Cesar [4 ]
Freitas-Castro, Felipe [5 ]
Fukutani, Kiyoshi Ferreira [1 ]
Donadi, Eduardo Antonio [4 ]
Cunha-Neto, Edecio [6 ]
Cunha, Thiago Mattar [7 ]
Silva, Joao Santana [1 ,8 ]
机构
[1] Univ Sao Paulo, Med Sch, Dept Biochem & Immunol Ribeirao Preto, Ribeirao Preto, SP, Brazil
[2] AC Camargo Canc Ctr, Int Res Ctr, Sao Paulo, Brazil
[3] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Clin Anal Toxicol & Food Sci, Ribeirao Preto, SP, Brazil
[4] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Med, Div Clin Immunol, Ribeirao Preto, SP, Brazil
[5] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Cell & Mol Biol, Ribeirao Preto, Brazil
[6] Univ Sao Paulo, Sch Med, Heart Inst, Lab Immunol, Sao Paulo, Brazil
[7] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Ribeirao Preto, SP, Brazil
[8] Univ Sao Paulo, Ribeirao Preto Med Sch, Fiocruz Biinst Translat Med Plataform, Ribeirao Preto, SP, Brazil
基金
巴西圣保罗研究基金会;
关键词
Trypanosoma cruzi; Chronic chagasic cardiomyopathy; PI3K gamma gene; Single nucleotide polymorphism; CLINICAL FORMS; DISEASE; INFECTION; IL-10; MICE;
D O I
10.1016/j.meegid.2020.104671
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
Chagas disease is caused by the protozoan parasite Trypanosoma cruzi. During the chronic phase of disease, while most infected people do not present symptoms, characterizing the asymptomatic form, some patients develop the cardiac form or chronic chagasic cardiomyopathy, which is considered the most severe manifestation of this disease. Considering that the activation of the PI3K gamma signaling pathway is essential for an efficient immune response against T. cruzi infection, we evaluated the PIK3CG C > T (rs1129293) polymorphism in exon 3 of this gene, which encodes the catalytic subunit of PI3K gamma. The PIK3CG CT and TT genotypes were found to be associated with an increased risk of developing the cardiac form of the disease rather than the asymptomatic or digestive forms. In conclusion, the presence of the T allele at single or double doses may differentiate the cardiac from other clinical manifestations of Chagas disease. This finding should help in further studies to evaluate the mechanisms underlying the differential association of PIK3CG in Chagas disease.
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