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.
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It seems likely that HLA DR4 (DRB1*04) was positively selected to overcome dengue hemorrhagic fever but not to stimulate rheumatoid arthritis and other autoimmune diseases in later life.
“Thus, it seems likely that HLA DR4 (DRB1*04) was positively selected to overcome dengue hemorrhagic fever but not to stimulate rheumatoid arthritis and other autoimmune diseases in later life.”
From Evolutionary medicine and chronic inflammatory state—known and new concepts in pathophysiology (2012) · cites this paper as [21]
HLA DR4 (DRB1*04) is a well-known risk factor for rheumatoid arthritis and other chronic autoimmune diseases, but also has a strong negative association with dengue hemorrhagic fever.
“HLA DR4 (DRB1*04) is a well-known risk factor for rheumatoid arthritis and other chronic autoimmune diseases, but HLA DR4 (DRB1*04) also has a strong negative association with dengue hemorrhagic fever [21].”
From Evolutionary medicine and chronic inflammatory state—known and new concepts in pathophysiology (2012) · cites this paper as [21]
HLA DR4 (DRB1*04) homozygous individuals are 12 times less likely to develop dengue hemorrhagic fever.
“HLA DR4 (DRB1*04) homozygous individuals are 12 times less likely to develop dengue hemorrhagic fever [21].”
From Evolutionary medicine and chronic inflammatory state—known and new concepts in pathophysiology (2012) · cites this paper as [21]
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- Authors
- LaFleur, C., Granados, J., Vargas-Alarcon, G., Ruíz-Morales, J., Villarreal-Garza, C., Higuera, L., Hernández-Pacheco, G., Cutiño-Moguel, T., Rangel, H., Figueroa, R., Acosta, M., Lazcano, E., & Ramos, C.
- Affiliations
- Instituto Nacional de Salud Pública (MX)
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (MX)
- Instituto Nacional de Cardiología (MX)
- Corresponding author
- Ramos, Celso
- Venue
- Human Immunology
- Publisher
- Elsevier BV
- Published
- 2002-11
- Volume
- 63
- Issue
- 11
- Pages
- 1039-1044
- ISSN
- 0198-8859 (ISSN-L)
- OpenAlex
- W2094150986
- Cited by
- 103
- References
- 27
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 4 · 2021: 1 · 2020: 6 · 2019: 6 · 2018: 2 · 2017: 2 · 2016: 7 · 2015: 4 · 2014: 4 · 2013: 7 · 2012: 8
- FWCI
- 1.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Mosquito-borne diseases and control
- Health Sciences › Medicine › Infectious Diseases › Viral Infections and Vectors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- HLA-DRB1*04, HLA-DR4, dengue hemorrhagic fever, dengue, genetic susceptibility, genetic resistance, major histocompatibility complex, secondary dengue infection, Mexican patients, positive selection
- MeSH terms
- Adolescent, Adult, Alleles, Child, Female, HLA-DR Antigens, Humans, Male, Middle Aged, HLA-DR4 Antigen, Severe Dengue, Genetic Predisposition to Disease, HLA-DRB1 Chains
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