title: Protective human leucocyte antigen haplotype, HLA-DRB1*01-B*14, against chronic Chagas disease in Bolivia.
abstract: 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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
authors.affiliation: Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN), and Global COE Program, Nagasaki University, Nagasaki, Japan.
authors.forename: Florencia
authors.initials: F
authors.lastname: del Puerto
authors.forename: Juan Eiki
authors.initials: JE
authors.lastname: Nishizawa
authors.forename: Mihoko
authors.initials: M
authors.lastname: Kikuchi
authors.forename: Yelin
authors.initials: Y
authors.lastname: Roca
authors.forename: Cinthia
authors.initials: C
authors.lastname: Avilas
authors.forename: Alberto
authors.initials: A
authors.lastname: Gianella
authors.forename: Javier
authors.initials: J
authors.lastname: Lora
authors.forename: Freddy Udalrico Gutierrez
authors.initials: FU
authors.lastname: Velarde
authors.forename: Sachio
authors.initials: S
authors.lastname: Miura
authors.forename: Norihiro
authors.initials: N
authors.lastname: Komiya
authors.forename: Koji
authors.initials: K
authors.lastname: Maemura
authors.forename: Kenji
authors.initials: K
authors.lastname: Hirayama
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001838:Bolivia; D014355:Chagas Disease / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D060467:Disease Resistance; D005260:Female; D005787:Gene Frequency; D059811:HLA-DRB1 Chains / Q000235:genetics* / Q000276:immunology*; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D014349:Trypanosoma cruzi / Q000276:immunology* / Q000472:pathogenicity
chemical_list: D059811:HLA-DRB1 Chains