Susceptibility to dengue hemorrhagic fever in vietnam: evidence of an association with variation in the vitamin d receptor and Fc gamma receptor IIa genes.
Loke H., Bethell D., Phuong CXT., Day N., White N., Farrar J., Hill A.
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 case-control 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 = 0.03). Homozygotes for the arginine variant at position 131 of the Fc gammaRIIA gene, who have less capacity to opsonize IgG2 antibodies, may also be protected from DHF (one-tailed P = 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.