Genotype of galectin 2 (LGALS2) is associated with insulin-glucose profile in the British Women’s Heart and Health Study

Christensen, Mikkel; Lawlor, Debbie A.; Gaunt, Tom R.; Howell, Martin W.; Smith, George Davey; Ebrahim, Shah; Day, Ian N.M.

doi:10.1007/s00125-006-0145-3

Cited by 13 publications

(7 citation statements)

References 17 publications

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“…Two loci were differentially methylated in offspring of women with past ED vs. controls, and these trended for significance following Bonferroni correction: cg05963962, corresponding to LOC84856 (LINC00839 a long intergenic non-protein coding element ) on chromosome 10, and cg11081833, corresponding to a soluble beta-galactoside binding lectin ( LGALS2 ) gene. This gene and its polymorphisms have been implicated in the metabolic syndrome [ 33 ], inflammation and immune response. Additional file 1 : Figure S3 and Figure S4 shows methylation levels across groups in these CpGs.…”

Section: Resultsmentioning

confidence: 99%

Maternal eating disorders affect offspring cord blood DNA methylation: a prospective study

et al. 2017

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BackgroundEating disorders (ED) are chronic psychiatric disorders, common amongst women of reproductive age. ED in pregnancy are associated with poor nutrition and abnormal intrauterine growth. Increasing evidence also shows offspring of women with ED have adverse developmental and birth outcomes. We sought to carry out the first study investigating DNA methylation in offspring of women with ED. We compared cord blood DNA methylation in offspring of women with active ED (n = 21), past ED (n = 43) and age- and social class-matched controls (n = 126) as part of the Avon Longitudinal Study of Parents and Children.ResultsOffspring of women with both active and past ED had lower whole-genome methylation compared to controls (active ED 49.1% (95% confidence intervals 50.5–47.7%), past ED 49.2% (95% CI 50.7–47.7.0%), controls 52.4% (95% CI 53.0%–51.0%)). Amongst offspring of ED women, those born to women with restrictive-type and purging-type ED had lower methylation levels compared to those of controls. Offspring of women with an active restrictive ED in pregnancy had lower whole-genome methylation compared to offspring of women with past restrictive ED. We observed decreased methylation at the DHCR24 locus in offspring of women with active pregnancy ED (effect size (ES) = − 0.124, p = 6.94 × 10−8) and increased methylation at the LGALS2 locus in offspring of women with past ED (ES = 0.07, p = 3.74 × 10−7) compared to controls.ConclusionsMaternal active and past ED are associated with differences in offspring whole-genome methylation. Our results show altered DNA methylation in loci relevant to metabolism; these might be biomarkers of disrupted metabolic pathways in offspring of ED mothers. Further work is needed to examine potential mechanisms and functional outcomes of the observed methylation patterns.Electronic supplementary materialThe online version of this article (10.1186/s13148-017-0418-3) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Maternal eating disorders affect offspring cord blood DNA methylation: a prospective study

et al. 2017

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“…Interestingly, in a search for genes associated with insulin resistance, a genotype of galectin-2, LGALS2 rs7291467, was stronger associated with changed fasting plasma glucose and serum insulin than other alleles were [ 26 ], and the same genotype which has a single-nucleotide polymorphism (3279C → T) in intron 1 of LGALS2 encoding galectin-2 was previously found to be significantly associated with myocardial infarction [ 27 ]. Galectin-2 binds to the proinflammatory cytokine lymphotoxin- α to regulate inflammation [ 27 ].…”

Section: Main Textmentioning

confidence: 99%

The Role of Galectins as Modulators of Metabolism and Inflammation

Brinchmann

Patel

Iversen

2018

Mediators of Inflammation

121

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Galectins are β-galcotosid-binding lectins. The function of galectins varies with their tissue-specific and subcellular location, and their binding to carbohydrates makes them key players in several intra- and extracellular processes where they bind to glycosylated proteins and lipids. In humans, there are 12 identified galectins, some with tissue-specific distribution. Galectins are found inside cells and in the nucleus, cytosol, and organelles, as well as extracellularly. Galectin-1, -2, -3, -4, -7, -8, -9, and -12 can all induce T-cell apoptosis and modulate inflammation. In the context of metabolic control and loss of the same in, for example, diabetes, galectin-1, -2, -3, -9, and -12 are especially interesting. This review presents information on galectins relevant to the control of inflammation and metabolism and the potential to target galectins for therapeutic purposes.

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“…The gene Lgals2 is the only QTL-associated gene that overlapped between our AS and DE gene list. Interestingly, a sequence variant in Lgals2 has been linked with altered plasma insulin and glucose levels in humans (Christensen et al 2006 ), underscoring its potential relevance in human T2D pathogenesis. The closely related gene Lgals3 has already been shown to protect from HFD-induced obesity in mice (Pejnovic et al 2013 ), but functional evidence for Lgals2 in context with T2D development is still missing.…”

Section: Discussionmentioning

confidence: 99%

Alternative exon splicing and differential expression in pancreatic islets reveals candidate genes and pathways implicated in early diabetes development

et al. 2021

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Type 2 diabetes (T2D) has a strong genetic component. Most of the gene variants driving the pathogenesis of T2D seem to target pancreatic β-cell function. To identify novel gene variants acting at early stage of the disease, we analyzed whole transcriptome data to identify differential expression (DE) and alternative exon splicing (AS) transcripts in pancreatic islets collected from two metabolically diverse mouse strains at 6 weeks of age after three weeks of high-fat-diet intervention. Our analysis revealed 1218 DE and 436 AS genes in islets from NZO/Hl vs C3HeB/FeJ. Whereas some of the revealed genes present well-established markers for β-cell failure, such as Cd36 or Aldh1a3, we identified numerous DE/AS genes that have not been described in context with β-cell function before. The gene Lgals2, previously associated with human T2D development, was DE as well as AS and localizes in a quantitative trait locus (QTL) for blood glucose on Chr.15 that we reported recently in our N2(NZOxC3H) population. In addition, pathway enrichment analysis of DE and AS genes showed an overlap of only half of the revealed pathways, indicating that DE and AS in large parts influence different pathways in T2D development. PPARG and adipogenesis pathways, two well-established metabolic pathways, were overrepresented for both DE and AS genes, probably as an adaptive mechanism to cope for increased cellular stress. Our results provide guidance for the identification of novel T2D candidate genes and demonstrate the presence of numerous AS transcripts possibly involved in islet function and maintenance of glucose homeostasis.

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Genotype of galectin 2 (LGALS2) is associated with insulin-glucose profile in the British Women’s Heart and Health Study

Cited by 13 publications

References 17 publications

Maternal eating disorders affect offspring cord blood DNA methylation: a prospective study

Maternal eating disorders affect offspring cord blood DNA methylation: a prospective study

The Role of Galectins as Modulators of Metabolism and Inflammation

Alternative exon splicing and differential expression in pancreatic islets reveals candidate genes and pathways implicated in early diabetes development

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