HLA-DR antigen frequencies in Mexican patients with dengue virus infection:: HLA-DR4 as a possible genetic resistance factor for dengue hemorrhagic fever

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 (C) American Society for Histocompatibility and Immunogenetics, 2002. Published by Elsevier Science Inc.