title: Contrasting associations of polymorphisms in FcγRIIa and DC-SIGN with the clinical presentation of dengue infection in a Mexican population.
abstract: 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.
authors.affiliation: Centro de Investigación Sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Av. Universidad 655, Col. Sta. María Ahuacatitlán, Cuernavaca 62100, Morelos, Mexico; U.S.-Mexico Fulbright-García Robles Commission for Educational and Cultural Exchange, Mexico City, Mexico.
authors.forename: Cecilia A
authors.initials: CA
authors.lastname: Noecker
authors.affiliation: Centro de Investigación Sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Av. Universidad 655, Col. Sta. María Ahuacatitlán, Cuernavaca 62100, Morelos, Mexico.
authors.forename: Irma Y
authors.initials: IY
authors.lastname: Amaya-Larios
authors.affiliation: Centro de Investigación Sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Av. Universidad 655, Col. Sta. María Ahuacatitlán, Cuernavaca 62100, Morelos, Mexico.
authors.forename: Marisol
authors.initials: M
authors.lastname: Galeana-Hernández
authors.affiliation: Centro de Investigación Sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Av. Universidad 655, Col. Sta. María Ahuacatitlán, Cuernavaca 62100, Morelos, Mexico; Organización Latinoamericana para el Fomento de la Investigación en Salud (OLFIS), Bucaramanga, Santander, Colombia; Center for Tropical Diseases, The University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: José
authors.initials: J
authors.lastname: Ramos-Castañeda
authors.affiliation: Centro de Investigación Sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Av. Universidad 655, Col. Sta. María Ahuacatitlán, Cuernavaca 62100, Morelos, Mexico; Organización Latinoamericana para el Fomento de la Investigación en Salud (OLFIS), Bucaramanga, Santander, Colombia. Electronic address: rutharam@yahoo.com.
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Martínez-Vega
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003715:Dengue / Q000276:immunology* / Q000473:pathology*; D004198:Disease Susceptibility; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics*; D008297:Male; D008800:Mexico; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000235:genetics*; D017452:Receptors, IgG / Q000235:genetics*; D012720:Severity of Illness Index; D055815:Young Adult; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D017452:Receptors, IgG; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C080568:Fc gamma receptor IIA
keywords: Case-control study; DC-SIGN; Dengue; FcγRIIa; SNP