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Age-related susceptibility to severe malaria associated with galectin-2 in highland Papuans.

ABSTRACT: 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.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.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.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.

SUBMITTER: Randall LM

PROVIDER: S-EPMC2880661 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

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Age-related susceptibility to severe malaria associated with galectin-2 in highland Papuans.

Randall Louise M LM Randall Louise M LM Kenangalem Enny E Lampah Daniel A DA Tjitra Emiliana E Mwaikambo Esther D ED Handojo Tjandra T Piera Kim A KA Zhao Zhen Zhen ZZ de Labastida Rivera Fabian F Zhou Yonghong Y McSweeney Karli M KM Le Lien L Amante Fiona H FH Haque Ashraful A Stanley Amanda C AC Woodberry Tonia T Salwati Ervi E Granger Donald L DL Hobbs Maurine R MR Price Ric N RN Weinberg J Brice JB Montgomery Grant W GW Anstey Nicholas M NM Engwerda Christian R CR

The Journal of infectious diseases 20100701 1

<h4>Background</h4>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.<h4>Methods</h4>We tested the association between rs7291467, a single-nucleotide polymorphism (SNP) in the LTalpha-related gene encoding gal ...[more]

PMID: 20500087

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Project description:BackgroundSenile osteoporosis with age-related bone loss is diagnosed depending on radiographic changes of bone and bone mineral density (BMD) measurement. However, radiographic alterations are usually signs of medium-late stage osteoporosis. Therefore, biomarkers have been proposed as indicators of bone loss. In the current study, Galectin-1 (Gal-1) showed age-related decline in mice serum. The role of Gal-1 in osteoporosis has not been investigated so far. Hence, the current study illustrated the relationship of serum Gal-1 level with bone loss.MethodsWe employed 6- and 18-month-old mice to establish an animal model of age-related trabecular bone loss, whose bone density and microstructure were investigated by micro-CT. ELISA was used to measure the levels of Gal-1 in serum. The correlation analysis was performed to illustrate the relationship between serum Gal-1 levels and trabecular bone loss. In addition, immunohistochemistry was used to investigate the abundance of Gal-1 in bone marrow of mice. ELISA and western blot were performed to measure the secretion ability and protein expression of Gal-1 in bone marrow stromal cells (BMSC), hematopoietic stem cells (HSC) and myeloid progenitor (MP) respectively. Flow cytometry was used to measure BMSC number in bone marrow. Finally, male volunteers with age-related BMD decrease were recruited and the relationship between serum Gal-1 and BMD was analyzed.ResultsGal-1 showed age-related decline in mice serum. Serum Gal-1 was positively associated with BV/TV of femur, tibia and L1 vertebrae in mice. BMSC secreted more Gal-1 compared with HSC and MP. BMSC number in bone marrow was significantly lower in aged mice compared with young mice. Significant attenuation of Gal-1 protein expression was observed in BMSC and HSC from aged mice compared with young mice. Further, we found a decline in serum Gal-1 levels in men with age-related BMD decrease. There was positive correlation between BMD and serum Gal-1 levels in these men.ConclusionsAge-related trabecular bone loss is associated with a decline in serum Gal-1 level in mice and men. Our study suggested Gal-1 had great potential to be a biomarker for discovering BMSC senescence, diagnosing early osteoporosis and monitoring trabecular bone loss.

Dataset Information

Age-related susceptibility to severe malaria associated with galectin-2 in highland Papuans.

Publications

Age-related susceptibility to severe malaria associated with galectin-2 in highland Papuans.

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