Dengue hemorrhagic fever is associated with polymorphisms in JAK1.
To identify genes associated with the clinical presentation of dengue, 50 cases of probable or possible dengue hemorrhagic fever (DHF), 236 dengue fever (DF), and 236 asymptomatic infections were genotyped for 593 single-nucleotide polymorphisms (SNPs) in 56 genes across the type 1 interferon (IFN) response pathway as well as other important candidate genes. By single locus analysis comparing DHF with DF, 11 of the 51 markers with P<0.05 were in the JAK1 gene. Five markers were significantly associated by false discovery rate criteria (q<0.20 when P<6 × 10(-4)). The JAK1 SNPs showed differential distribution by ethnicity and ancestry consistent with epidemiologic observations in the Americas. The association remained significant after controlling for ancestry and income. No association was observed with markers in the gene encoding CD209 (DC-SIGN). An association between DHF and JAK1 polymorphisms is in agreement with expression profiles showing generalized decreased type 1 IFN-stimulated gene expression in these patients.
Silva
Luciano K
LK
Fundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz, Laboratory of Pathology and Molecular Biology, Rua Waldemar Falcão, Candeal, Salvador, Bahia, Brazil.
Blanton
Ronald E
RE
Parrado
Antonio R
AR
Melo
Paulo S
PS
Morato
Vanessa G
VG
Reis
Eliana A G
EA
Dias
Juarez P
JP
Castro
Jesuina M
JM
Vasconcelos
Pedro F C
PF
Goddard
Katrina A B
KA
Barreto
Maurício L
ML
Reis
Mitermayer G
MG
Teixeira
M Glória
MG
D000293:Adolescent; D000328:Adult; D044383:Black People / Q000235:genetics; D001938:Brazil / Q000453:epidemiology; D002648:Child; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007199:Indians, South American / Q000235:genetics; D053613:Janus Kinase 1 / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D019595:Severe Dengue / Q000208:ethnology / Q000235:genetics*; D044465:White People / Q000235:genetics; D055815:Young Adult
D053613:Janus Kinase 1