title: Association of BAK1 single nucleotide polymorphism with a risk for dengue hemorrhagic fever.
abstract: Dengue hemorrhagic fever (DHF) is a severe life-threatening form of dengue infection. Low platelet count is one of the characteristic clinical manifestations in patients with severe dengue. However, little is known about genetic factors in the host that cause low platelet count in patients with dengue.
  
  
  
  A previous genome-wide association study of hematological and biochemical traits identified single nucleotide polymorphisms (SNPs) associated with low platelet count in healthy subjects. To examine the possible association of these SNPs with DHF, 918 Thai patients with dengue [509 patients with DHF and 409 with dengue fever (DF)] were genotyped for five SNPs: rs5745568 in BAK1, rs6141 in THPO, rs6065 in GP1BA, rs739496 in SH2B3, and rs385893 in RCL1. In addition, rs4804803 in CD209, that has been reported to be associated with dengue infection, was also genotyped to examine if rs4804803 affects the association detected in this study.
  
  
  
  The allele frequencies of each SNP were compared between the DHF and DF groups. Among the five SNPs, the G allele of rs5745568 in BAK1 was significantly associated with a risk for DHF [P = 0.006 and crude odd ratio (95 % confidence interval) = 1.32 (1.09-1.60)]. The association of this allele with DHF was also significant in a logistic regression analysis adjusted for age, sex, hospital (i.e., geographic region), immune status (i.e., primary or secondary infection), and virus serotype [P = 0.016 and adjusted odd ratio (95 % confidence interval) = 1.29 (1.05-1.58)]. The result was not influenced by rs4804803 [P = 0.0167 and adjusted OR (95 % CI) = 1.29 (1.05-1.58)]. No other SNPs including rs4804803 showed significant association.
  
  
  
  The low-level constitutive production of platelets caused by the G allele of rs5745568 seems to increase the risk of bleeding in dengue infection. Our results suggest that BCL-2 homologous antagonist/killer (BAK) protein, encoded by BAK1, plays a crucial role in the pathogenesis of DHF.
authors.affiliation: Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.|Faculty of Public Health, University of Medicine and Pharmacy at Ho Chi Minh city, Ho Chi Minh City, Viet Nam.
authors.forename: Tran Ngoc
authors.initials: TN
authors.lastname: Dang
authors.affiliation: Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.|Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.|Graduate School of Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Izumi
authors.initials: I
authors.lastname: Naka
authors.affiliation: Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand.
authors.forename: Areerat
authors.initials: A
authors.lastname: Sa-Ngasang
authors.affiliation: Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand.
authors.forename: Surapee
authors.initials: S
authors.lastname: Anantapreecha
authors.affiliation: Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand.
authors.forename: Nuanjun
authors.initials: N
authors.lastname: Wichukchinda
authors.affiliation: Food and Drug Administration, Ministry of Public Heath, Nonthaburi, Thailand.
authors.forename: Pathom
authors.initials: P
authors.lastname: Sawanpanyalert
authors.affiliation: Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: Jintana
authors.initials: J
authors.lastname: Patarapotikul
authors.affiliation: Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.|Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Tsuchiya
authors.affiliation: Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan. juno-tky@umin.ac.jp.|Faculty of Medicine, University of Tsukuba, Tsukuba, Japan. juno-tky@umin.ac.jp.|Graduate School of Science, The University of Tokyo, Tokyo, Japan. juno-tky@umin.ac.jp.
authors.forename: Jun
authors.initials: J
authors.lastname: Ohashi
mesh_terms: D000293:Adolescent; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D016015:Logistic Models; D016017:Odds Ratio; D010976:Platelet Count; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D019595:Severe Dengue / Q000235:genetics* / Q000473:pathology; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000235:genetics*
chemical_list: C494772:BAK1 protein, human; D050998:bcl-2 Homologous Antagonist-Killer Protein