RESUMO
BACKGROUND: Chagas disease, caused by the flagellate parasite Trypanosoma cruzi affects 8-10 million people in Latin America. The mechanisms that underlie the development of complications of chronic Chagas disease, characterized primarily by pathology of the heart and digestive system, are not currently understood. To identify possible host genetic factors that may influence the clinical course of Chagas disease, Human Leucocyte Antigen (HLA) regional gene polymorphism was analyzed in patients presenting with differing clinical symptoms. METHODOLOGY: Two hundred and twenty nine chronic Chagas disease patients in Santa Cruz, Bolivia, were examined by serological tests, electrocardiogram (ECG), and Barium enema colon X-ray. 31.4% of the examinees showed ECG alterations, 15.7% megacolon and 58.1% showed neither of them. A further 62 seropositive megacolon patients who had undergone colonectomy due to acute abdomen were recruited. We analyzed their HLA genetic polymorphisms (HLA-A, HLA-B, MICA, MICB, DRB1 and TNF-alpha promoter region) mainly through Sequence based and LABType SSO typing test using LUMINEX Technology. PRINCIPAL FINDINGS: The frequencies of HLA-DRB1*01 and HLA-B*14:02 were significantly lower in patients suffering from megacolon as well as in those with ECG alteration and/or megacolon compared with a group of patients with indeterminate symptoms. The DRB1*0102, B*1402 and MICA*011 alleles were in strong Linkage Disequilibrium (LD), and the HLA-DRB1*01-B*14-MICA*011 haplotype was associated with resistance against chronic Chagas disease. CONCLUSIONS: This is the first report of HLA haplotype association with resistance to chronic Chagas disease.
Assuntos
Doença de Chagas/genética , Doença de Chagas/imunologia , Resistência à Doença , Cadeias HLA-DRB1/genética , Cadeias HLA-DRB1/imunologia , Polimorfismo Genético , Trypanosoma cruzi/imunologia , Adulto , Idoso , Animais , Bolívia , Doença de Chagas/patologia , Feminino , Frequência do Gene , Haplótipos , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Trypanosoma cruzi/patogenicidadeRESUMO
BACKGROUND: The causative agent of Chagas disease, Trypanosoma cruzi, is divided into 6 Discrete Typing Units (DTU): Tc I, IIa, IIb, IIc, IId and IIe. In order to assess the relative pathogenicities of different DTUs, blood samples from three different clinical groups of chronic Chagas disease patients (indeterminate, cardiac, megacolon) from Bolivia were analyzed for their circulating parasites lineages using minicircle kinetoplast DNA polymorphism. METHODS AND FINDINGS: Between 2000 and 2007, patients sent to the Centro Nacional de Enfermedades Tropicales for diagnosis of Chagas from clinics and hospitals in Santa Cruz, Bolivia, were assessed by serology, cardiology and gastro-intestinal examinations. Additionally, patients who underwent colonectomies due to Chagasic magacolon at the Hospital Universitario Japonés were also included. A total of 306 chronic Chagas patients were defined by their clinical types (81 with cardiopathy, 150 without cardiopathy, 100 with megacolon, 144 without megacolon, 164 with cardiopathy or megacolon, 73 indeterminate and 17 cases with both cardiopathy and megacolon). DNA was extracted from 10 ml of peripheral venous blood for PCR analysis. The kinetoplast minicircle DNA (kDNA) was amplified from 196 out of 306 samples (64.1%), of which 104 (53.3%) were Tc IId, 4 (2.0%) Tc I, 7 (3.6%) Tc IIb, 1 (0.5%) Tc IIe, 26 (13.3%) Tc I/IId, 1 (0.5%) Tc I/IIb/IId, 2 (1.0%) Tc IIb/d and 51 (25.9%) were unidentified. Of the 133 Tc IId samples, three different kDNA hypervariable region patterns were detected; Mn (49.6%), TPK like (48.9%) and Bug-like (1.5%). There was no significant association between Tc types and clinical manifestations of disease. CONCLUSIONS: None of the identified lineages or sublineages was significantly associated with any particular clinical manifestations in the chronic Chagas patients in Bolivia.
Assuntos
Doença de Chagas/patologia , Doença de Chagas/parasitologia , DNA de Cinetoplasto/genética , DNA de Protozoário/genética , Polimorfismo Genético , Trypanosoma cruzi/classificação , Trypanosoma cruzi/patogenicidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bolívia , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Trypanosoma cruzi/genética , Trypanosoma cruzi/isolamento & purificação , Adulto JovemRESUMO
El propósito de este estudio es determinar si el envejecimiento influye sobre la vulnerabilidad auricular inducida por la estimulación auricular programada en pacientes con fibrilación auricular paroxística idiopática. La investigación incluyó a 148 pacientes, de los cuales 78 tenían fibrilación auricular paroxística idiopática y 70 eran pacientes control. Para determinar los efectos de la edad sobre la vulnerabilidad auricular, dividimos a los pacientes con fibrilación auricular en dos grupos: el grupo mayor tuvo 38 pacientes ®g60 años de edad y el grupo más joven tuvo 40 pacientes <60 años de edad. Los siguientes parámetros de vulnerabilidad auricular fueron estudiados y medidos cuantitativamente: 1) el período refractario efectivo auricular, 2) la zona del retardo de la conducción auricular, y 3) el máximo retardo en la conducción auricular. El período refractario efectivo auricular promedio del grupo más joven (201±28 msec) fue significativamente más corto que el del grupo mayor de edad (215±27 msec, p<0.05) y que el del grupo control (215± 29 msec. p<0.02). La zona del retardo en la conducción auricular promedio del grupo mayor (50±25 msec) y la del grupo más joven (50±31 msec) fueron significativamente más amplias que la del grupo control (34±22 msec) (p<0.01). El máximo retardo en la conducción auricular del grupo mayor (65±31 msec) y el del grupo más joven (58±27 msec) fueron significativamente más amplios que el del grupo control (43±20 msec) (p<0.01). Por lo tanto, si bien el retardo en la conducción auricular se observa tanto en los pacientes más jóvenes como en los mayores de edad, el período refractario efectivo auricular es más corto en los pacientes más jóvenes con fibrilación auricular paroxística idiopática. Estos resultados sugieren diferencias dependientes de la edad en la fisiopatología de la fibrilación auricular