Contrasting associations of polymorphisms in FcγRIIa and DC-SIGN with the clinical presentation of dengue infection in a Mexican population.

Dengue virus (DENV) causes a spectrum of illness from asymptomatic infection, to a mild febrile illness, to occasional more severe complications including hemorrhage and shock. Dengue is endemic in the state of Morelos, Mexico. Two single nucleotide polymorphisms (SNPs), rs1801274 of FcγRIIa and rs4804803 of DC-SIGN, have been associated with protection from or susceptibility to severe dengue infection. Both of these polymorphisms are located in genes for receptors with important roles in dengue pathogenesis, and their relationship with the clinical presentation of dengue infection in Mexican populations is unknown. In this study, real-time PCR was used to characterize the distribution of rs1801274 and rs4804803 in subjects with asymptomatic dengue infection (n=145), uncomplicated dengue (n=67), and severe dengue (n=36) in Morelos. In contrast with previous studies, the histidine (A) variant of rs1801274 was associated with more mild infection: carrying the histidine allele (either homozygous or heterozygous) was associated with protection from symptomatic infection compared with asymptomatic (OR 0.51, p=0.038). Histidine homozygotes were also less likely to present severe dengue (OR 0.34, p=0.05). Logistic regression models confirm this association (OR 0.48, p=0.04) and also indicate that the G allele of rs4804803 is associated with symptomatic dengue (OR 2.3, p=0.08), after accounting for other biological factors including history of infection. This variant was rare in this study population, with a frequency of 5.4%. These findings reflect the complexity of influences on the development of severe dengue infection. The inclusion of asymptomatic infections and adjusted case definitions likely do not explain the entire disparity with previous findings. Interactions with other polymorphisms may explain why the association of rs1801274 is reversed in this population compared to others. This study demonstrates the importance of genetic association studies in multiple genetically distinct populations.

Seroprevalence of neutralizing antibodies against dengue virus in two localities in the state of Morelos, Mexico.

Humoral immune response against dengue virus (DENV) is an important component in dengue-endemic transmission. We conducted a cross-sectional nested cohort study to determine the seroprevalence and frequency of neutralizing antibodies against DENV serotypes in two endemic localities in the state of Morelos, Mexico. The cohort participants (N = 1,196) were screened to determine previous exposure to DENV. Overall seroprevalence was 76.6% (95% confidence interval [95% CI] = 73.6-79.2), and prevalence of neutralizing antibodies in the 5- to 9-year-old group was 82.5% (95% CI = 67.2-92.7), 45% (95% CI = 29.3-61.5), and 65% (95% CI = 48.3-79.4) for DENV-1, DENV-2, and DENV-3, respectively. For participants older than 10 years, the observed seroprevalence was above 60% for each serotype, except DENV-4 in the 10- to 25-year-old group (42.9%); 81% of humoral responses were multitypic. The outcomes of our study contribute to understanding the immune component of dengue transmission and provide focal information for the evaluation of vaccine candidates under development.