title: Age-related susceptibility to severe malaria associated with galectin-2 in highland Papuans.
abstract: BACKGROUND
  Age and host genetics are important determinants of malaria severity. Lymphotoxin-alpha (LTalpha) has been associated with the development of cerebral malaria (CM) and other severe malaria (SM) syndromes. Mutations in genes regulating LTalpha production contribute to other acute vascular diseases and may contribute to malaria pathogenesis.
  
  
  METHODS
  We tested the association between rs7291467, a single-nucleotide polymorphism (SNP) in the LTalpha-related gene encoding galectin-2 (LGALS2), disease severity, and function in a case-control study of ethnic Highland Papuan adults and children with SM (n = 380) and asymptomatic malaria-exposed controls (n = 356) originating from a non-malaria-endemic region but residing in a lowland malaria-endemic area of Papua, Indonesia.
  
  
  RESULTS
  The LGALS2 SNP showed a significant association with susceptibility to SM (including CM), in children (odds ratio, 2.02 [95% confidence interval, 1.14-3.57]) but not in adults. In SM, the C allele at rs7291467 was associated with enhanced galectin-2 transcript levels. In a separate group of Tanzanian children originating from a malaria-endemic region, we found preservation of the major ancestral LGALS2 allele and no association with susceptibility to CM.
  
  
  CONCLUSIONS
  Results suggest differences in the inflammatory contribution to the development of SM between children and adults in the same population and potential differences between individuals originating from malaria-endemic and non-malaria-endemic areas.
authors.affiliation: Queensland Institute of Medical Research and Australian Centre for Vaccine Development, and The University of Queensland, School of Population Health, Herston, Queensland, Australia.
authors.forename: Louise M
authors.initials: LM
authors.lastname: Randall
authors.forename: Enny
authors.initials: E
authors.lastname: Kenangalem
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Lampah
authors.forename: Emiliana
authors.initials: E
authors.lastname: Tjitra
authors.forename: Esther D
authors.initials: ED
authors.lastname: Mwaikambo
authors.forename: Tjandra
authors.initials: T
authors.lastname: Handojo
authors.forename: Kim A
authors.initials: KA
authors.lastname: Piera
authors.forename: Zhen Zhen
authors.initials: ZZ
authors.lastname: Zhao
authors.forename: Fabian
authors.initials: F
authors.lastname: de Labastida Rivera
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Zhou
authors.forename: Karli M
authors.initials: KM
authors.lastname: McSweeney
authors.forename: Lien
authors.initials: L
authors.lastname: Le
authors.forename: Fiona H
authors.initials: FH
authors.lastname: Amante
authors.forename: Ashraful
authors.initials: A
authors.lastname: Haque
authors.forename: Amanda C
authors.initials: AC
authors.lastname: Stanley
authors.forename: Tonia
authors.initials: T
authors.lastname: Woodberry
authors.forename: Ervi
authors.initials: E
authors.lastname: Salwati
authors.forename: Donald L
authors.initials: DL
authors.lastname: Granger
authors.forename: Maurine R
authors.initials: MR
authors.lastname: Hobbs
authors.forename: Ric N
authors.initials: RN
authors.lastname: Price
authors.forename: J Brice
authors.initials: JB
authors.lastname: Weinberg
authors.forename: Grant W
authors.initials: GW
authors.lastname: Montgomery
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Anstey
authors.forename: Christian R
authors.initials: CR
authors.lastname: Engwerda
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D037501:Galectin 2 / Q000235:genetics*; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D007214:Indonesia / Q000453:epidemiology; D007223:Infant; D007438:Introns; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D037501:Galectin 2; D005819:Genetic Markers