Susceptibility to dengue hemorrhagic fever in vietnam: evidence of an association with variation in the vitamin d receptor and Fc gamma receptor IIa genes.

Abstract

Abstract. Dengue is an increasingly important cause of morbidity and mortality in the tropics, with more than a billion people at risk each year. Immunologic enhancement is thought to contribute to disease pathogenesis. Only a very small proportion of infected individuals develop life-threatening dengue hemorrhagic fever (DHF). In a large casecontrol study with 400 DHF patients and 300 matched controls, we have assessed five polymorphic non-HLA host genetic factors that might influence susceptibility to DHF. The less frequent t allele of a variant at position 352 of the vitamin D receptor (VDR) gene was associated with resistance to severe dengue (P ‫ס‬ 0.03). Homozygotes for the arginine variant at position 131 of the Fc␥RIIA gene, who have less capacity to opsonize IgG2 antibodies, may also be protected from DHF (one-tailed P ‫ס‬ 0.03). No associations were found with polymorphisms in the mannose binding lectin, interleukin-1 (IL-4), and IL-1 receptor antagonist genes. Further studies to confirm these associations are warranted.

The pathogenesis of dengue

“…90 The vitamin D receptor modulates the immune response by stimulating cell-mediated immunity and inhibiting lymphocyte proliferation; a polymorphism in the receptor appears to protect against severe dengue. 94 The Fc receptor mediates entry of antibody-coated DENV into target cells; the same study demonstrated that homozygotes for the arginine variant at position 131 of the Fc receptor gene may also be protected from severe disease. 94 This is perhaps because these homozygotes have less ability to opsonise IgG2 antibodies.…”

“…94 The Fc receptor mediates entry of antibody-coated DENV into target cells; the same study demonstrated that homozygotes for the arginine variant at position 131 of the Fc receptor gene may also be protected from severe disease. 94 This is perhaps because these homozygotes have less ability to opsonise IgG2 antibodies. There have been conflicting results from studies looking at polymorphisms in the TNF- gene -data from Vietnam did not show an association, whereas investigators in Venezuela reported a significantly increased prevalence of the TNF-308A allele in patients with severe dengue.…”

“…There have been conflicting results from studies looking at polymorphisms in the TNF- gene -data from Vietnam did not show an association, whereas investigators in Venezuela reported a significantly increased prevalence of the TNF-308A allele in patients with severe dengue. 94,95 Dengue infection of dendritic cells is mediated by the attachment factor, dendritic cell-specific ICAM-3 grabbing nonintegrin (DC-SIGN1, encoded by CD209). The G allele of the variant of the promoter region (DC-SIGN-336) was associated with protection against dengue fever, but not dengue haemorrhagic fever.…”

Dengue: a continuing global threat

“…Host factors that increase the risk of severe dengue disease include female sex, several human leukocyte antigen (HLA) class I alleles, a promoter variant of the DC-SIGN receptor gene, a single-nucleotide polymorphism in the tumour necrosis factor (TNF) gene and AB blood group [31][32][33][34][35][36] . Host factors that reduce the risk of severe disease during a second dengue infection include race, second or third degree malnutrition, and polymorphisms in the Fcγ receptor and vitamin D receptor genes [37][38][39][40][41][42] . Secondary dengue infections in adults can produce the classical DSS or severe disease complicated by haemorrhages.…”

Association of human leukocyte antigen DQ1 and dengue fever in a white Southern Brazilian population

“…Warm and humid climate, population density, and housing aspects also influence disease outbreaks. Nevertheless, little information is available on the influence of genetic factors for dengue infection susceptibility (Loke et al 2002).…”