title: Combination of CTLA-4 and TGFbeta1 gene polymorphisms associated with dengue hemorrhagic fever and virus load in a dengue-2 outbreak.
abstract: The pathogenesis of dengue hemorrhagic fever (DHF) has been considered to be massive immune activation of T cells. Abnormal expression of the immune regulatory molecules, CTLA-4 and TGFbeta1, leads to disturbances of regulatory T cell immune response. We investigate the contribution of CTLA-4 and TGFbeta1 in DHF by analyzing them for association with virus load in blood and polymorphisms of CTLA-4 +49A/G, and TGFbeta1 -509C/T in a DEN-2 outbreak. The increased frequency of the TGFbeta1 -509 CC genotype in patients with DHF was compared to those with dengue fever (OR=1.9, p=0.034). Moreover, the presence of the CTLA-4 +49 G allele and TGFbeta1 -509 CC genotype increased the susceptibility to risk of DHF (OR=2.1, p=0.028) and significantly higher virus load (p=0.013). This finding suggests that a combination of CTLA-4 and TGFbeta1 polymorphisms is associated with the susceptibility of DHF and higher virus load.
authors.affiliation: Department of Medical Research, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University, Kaohsiung, Taiwan.
authors.forename: Rong-Fu
authors.initials: RF
authors.lastname: Chen
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Jiin-Tsuey
authors.initials: JT
authors.lastname: Cheng
authors.forename: Hau
authors.initials: H
authors.lastname: Chuang
authors.forename: Jen-Chieh
authors.initials: JC
authors.lastname: Chang
authors.forename: Jien-Wei
authors.initials: JW
authors.lastname: Liu
authors.forename: I-Chun
authors.initials: IC
authors.lastname: Lin
authors.forename: Kuender D
authors.initials: KD
authors.lastname: Yang
mesh_terms: D000483:Alleles; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D060908:CTLA-4 Antigen; D004196:Disease Outbreaks; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D019595:Severe Dengue / Q000196:embryology / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000378:metabolism; D019562:Viral Load
chemical_list: D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D053773:Transforming Growth Factor beta1