Age-Related susceptibility to severe Malaria associated with Galectin-2 in Highland Papuans

Louise Randall; Enny Kenangalem; Daniel Lampah; Emiliana Tjitra; Esther Mwaikambo; Tjandra Handojo; Kim Piera; Zhen Zhen Zhao; Fabian de Labastida Rivera; Yonghong Zhou; Karli McSweeney; Lien Le; Fiona Amante; Ashraful Haque; Amanda Stanley; Tonia Woodberry; Ervi Salwati; Donald Granger; Maurine Hobbs; Ric Price; J Brice Weinberg; Grant Montgomery; Nicholas Anstey; Christian Engwerda

doi:10.1086/653125

Age-Related susceptibility to severe Malaria associated with Galectin-2 in Highland Papuans

Louise Randall, Enny Kenangalem, Daniel Lampah, Emiliana Tjitra, Esther Mwaikambo, Tjandra Handojo, Kim Piera, Zhen Zhen Zhao, Fabian de Labastida Rivera, Yonghong Zhou, Karli McSweeney, Lien Le, Fiona Amante, Ashraful Haque, Amanda Stanley, Tonia Woodberry, Ervi Salwati, Donald Granger, Maurine Hobbs, Ric PriceJ Brice Weinberg, Grant Montgomery, Nicholas Anstey, Christian Engwerda

Global and Tropical Health

Research output: Contribution to journal › Article › peer-review

Abstract

Background: Age and host genetics are important determinants of malaria severity. Lymphotoxin-? (LT?) has been associated with the development of cerebral malaria (CM) and other severe malaria (SM) syndromes. Mutations in genes regulating LTa 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 LT?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 malariaendemic and non-malaria-endemic areas.

Original language	English
Pages (from-to)	117-124
Number of pages	8
Journal	Journal of Infectious Diseases
Volume	202
DOIs	https://doi.org/10.1086/653125
Publication status	Published - 1 Jul 2010

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Randall, L., Kenangalem, E., Lampah, D., Tjitra, E., Mwaikambo, E., Handojo, T., Piera, K., Zhao, Z. Z., Rivera, F. D. L., Zhou, Y., McSweeney, K., Le, L., Amante, F., Haque, A., Stanley, A., Woodberry, T., Salwati, E., Granger, D., Hobbs, M., ... Engwerda, C. (2010). Age-Related susceptibility to severe Malaria associated with Galectin-2 in Highland Papuans. Journal of Infectious Diseases, 202, 117-124. https://doi.org/10.1086/653125

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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-? (LT?) has been associated with the development of cerebral malaria (CM) and other severe malaria (SM) syndromes. Mutations in genes regulating LTa 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 LT?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 malariaendemic and non-malaria-endemic areas. ",

keywords = "galectin 2, lymphotoxin, lymphotoxin related gene encoding galectin 2, unclassified drug, adolescent, adult, age distribution, aged, allele, article, brain malaria, controlled study, disease predisposition, disease severity, endemic disease, female, gene expression, human, Indonesia, intron, major clinical study, male, mutational analysis, population research, priority journal, single nucleotide polymorphism, case control study, child, genetic marker, genetic predisposition, genetics, infant, malaria falciparum, middle aged, preschool child, Adolescent, Adult, Age Distribution, Aged, Case-Control Studies, Child, Child, Preschool, Galectin 2, Genetic Markers, Genetic Predisposition to Disease, Humans, Infant, Introns, Malaria, Falciparum, Middle Aged, Polymorphism, Single Nucleotide, Young Adult",

author = "Louise Randall and Enny Kenangalem and Daniel Lampah and Emiliana Tjitra and Esther Mwaikambo and Tjandra Handojo and Kim Piera and Zhao, {Zhen Zhen} and Rivera, {Fabian de Labastida} and Yonghong Zhou and Karli McSweeney and Lien Le and Fiona Amante and Ashraful Haque and Amanda Stanley and Tonia Woodberry and Ervi Salwati and Donald Granger and Maurine Hobbs and Ric Price and Weinberg, {J Brice} and Grant Montgomery and Nicholas Anstey and Christian Engwerda",

year = "2010",

month = jul,

day = "1",

doi = "10.1086/653125",

language = "English",

volume = "202",

pages = "117--124",

journal = "Journal of Infectious Diseases",

issn = "0022-1899",

publisher = "Oxford University Press",

}

Randall, L, Kenangalem, E, Lampah, D, Tjitra, E, Mwaikambo, E, Handojo, T, Piera, K, Zhao, ZZ, Rivera, FDL, Zhou, Y, McSweeney, K, Le, L, Amante, F, Haque, A, Stanley, A, Woodberry, T, Salwati, E, Granger, D, Hobbs, M, Price, R, Weinberg, JB, Montgomery, G, Anstey, N & Engwerda, C 2010, 'Age-Related susceptibility to severe Malaria associated with Galectin-2 in Highland Papuans', Journal of Infectious Diseases, vol. 202, pp. 117-124. https://doi.org/10.1086/653125

TY - JOUR

T1 - Age-Related susceptibility to severe Malaria associated with Galectin-2 in Highland Papuans

AU - Randall, Louise

AU - Kenangalem, Enny

AU - Lampah, Daniel

AU - Tjitra, Emiliana

AU - Mwaikambo, Esther

AU - Handojo, Tjandra

AU - Piera, Kim

AU - Zhao, Zhen Zhen

AU - Rivera, Fabian de Labastida

AU - Zhou, Yonghong

AU - McSweeney, Karli

AU - Le, Lien

AU - Amante, Fiona

AU - Haque, Ashraful

AU - Stanley, Amanda

AU - Woodberry, Tonia

AU - Salwati, Ervi

AU - Granger, Donald

AU - Hobbs, Maurine

AU - Price, Ric

AU - Weinberg, J Brice

AU - Montgomery, Grant

AU - Anstey, Nicholas

AU - Engwerda, Christian

PY - 2010/7/1

Y1 - 2010/7/1

N2 - Background: Age and host genetics are important determinants of malaria severity. Lymphotoxin-? (LT?) has been associated with the development of cerebral malaria (CM) and other severe malaria (SM) syndromes. Mutations in genes regulating LTa 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 LT?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 malariaendemic and non-malaria-endemic areas.

AB - Background: Age and host genetics are important determinants of malaria severity. Lymphotoxin-? (LT?) has been associated with the development of cerebral malaria (CM) and other severe malaria (SM) syndromes. Mutations in genes regulating LTa 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 LT?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 malariaendemic and non-malaria-endemic areas.

KW - galectin 2

KW - lymphotoxin

KW - lymphotoxin related gene encoding galectin 2

KW - unclassified drug

KW - adolescent

KW - adult

KW - age distribution

KW - aged

KW - allele

KW - article

KW - brain malaria

KW - controlled study

KW - disease predisposition

KW - disease severity

KW - endemic disease

KW - female

KW - gene expression

KW - human

KW - Indonesia

KW - intron

KW - major clinical study

KW - male

KW - mutational analysis

KW - population research

KW - priority journal

KW - single nucleotide polymorphism

KW - case control study

KW - child

KW - genetic marker

KW - genetic predisposition

KW - genetics

KW - infant

KW - malaria falciparum

KW - middle aged

KW - preschool child

KW - Adolescent

KW - Adult

KW - Age Distribution

KW - Aged

KW - Case-Control Studies

KW - Child

KW - Child, Preschool

KW - Galectin 2

KW - Genetic Markers

KW - Genetic Predisposition to Disease

KW - Humans

KW - Infant

KW - Introns

KW - Malaria, Falciparum

KW - Middle Aged

KW - Polymorphism, Single Nucleotide

KW - Young Adult

UR - http://www.scopus.com/inward/record.url?scp=77953721831&partnerID=8YFLogxK

U2 - 10.1086/653125

DO - 10.1086/653125

M3 - Article

SN - 0022-1899

VL - 202

SP - 117

EP - 124

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

ER -

Age-Related susceptibility to severe Malaria associated with Galectin-2 in Highland Papuans

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