title: HLA-DR antigen frequencies in Mexican patients with dengue virus infection: HLA-DR4 as a possible genetic resistance factor for dengue hemorrhagic fever.
abstract: The human leukocyte antigen DRB1 locus (HLA-DRB1) was typed in genomic DNA extracted from whole blood samples of 34 Mexican dengue hemorrhagic fever (DHF) patients and 47 dengue fever (DF) patients, by polymerase chain reaction-sequence-specific oligonucleotide reverse dot blot. HLA-DRB1*04 was negatively associated with risk of DHF (OR 0.31, 95% CI 0.11-0.85). HLA-DR4 homozygous individuals were 11.6 times less likely to develop DHF in comparison to DR4 negative persons (OR 0.08, 95% CI 0.01-0.75). After adjusting for gender and infection type by logistic regression, DR4 positive individuals were 3.6 times less likely to develop DHF than DR4 negative persons (OR 0.28, 95% CI 0.12-0.66). A secondary dengue virus infection was also positively linked with DHF risk (OR 2.89, 95% CI 0.92-9.07). This data suggests that genes of the major histocompatibility complex play a major role in the susceptibility and/or resistance to develop DHF. In Mexicans, HLA-DR4 may be a genetic factor that is protective against DHF. Because HLA-DR4 has been positively selected in Latin American populations, these results may apply also to other similar ethnic groups, particularly those with high percentages of admixture with indigenous Amerindian genes.
authors.affiliation: Centro de Investigaciones sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pùblica, Cuernavaca, Morelos, Mexico.
authors.forename: Curtis
authors.initials: C
authors.lastname: LaFleur
authors.forename: Julio
authors.initials: J
authors.lastname: Granados
authors.forename: Gilberto
authors.initials: G
authors.lastname: Vargas-Alarcon
authors.forename: Jorge
authors.initials: J
authors.lastname: Ruíz-Morales
authors.forename: Cynthia
authors.initials: C
authors.lastname: Villarreal-Garza
authors.forename: Lorena
authors.initials: L
authors.lastname: Higuera
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Hernández-Pacheco
authors.forename: Teresa
authors.initials: T
authors.lastname: Cutiño-Moguel
authors.forename: Hilda
authors.initials: H
authors.lastname: Rangel
authors.forename: Raymunda
authors.initials: R
authors.lastname: Figueroa
authors.forename: Maribel
authors.initials: M
authors.lastname: Acosta
authors.forename: Eduardo
authors.initials: E
authors.lastname: Lazcano
authors.forename: Celso
authors.initials: C
authors.lastname: Ramos
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease; D006684:HLA-DR Antigens / Q000235:genetics*; D015804:HLA-DR4 Antigen / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D008875:Middle Aged; D019595:Severe Dengue / Q000235:genetics / Q000276:immunology*
chemical_list: D006684:HLA-DR Antigens; D015804:HLA-DR4 Antigen; D059811:HLA-DRB1 Chains