Disease relevance of LGALS2

• Functional variation in LGALS2 confers risk of myocardial infarction and regulates lymphotoxin-alpha secretion in vitro [1].
• Effects of lymphotoxin-alpha gene and galectin-2 gene polymorphisms on inflammatory biomarkers, cellular adhesion molecules and risk of coronary heart disease [2].
• Several genetic and clinical studies implicate LTalpha, and its binding and regulatory partner galectin-2, as a risk factor in the pathogenesis of cardiovascular diseases including miocardial infarction, aortic aneurysm, and cerebral infarction [3].

High impact information on LGALS2

• Genome-wide association studies have also been undertaken, and the pro-inflammatory cytokine lymphotoxin-alpha (LTA), and its key ligand galectin-2 (LGALS2) have been identified as genes implicated in predisposition for heart attack [4].
• Galectin-2 is structurally closely related to galectin-1, but has a distinct expression profile primarily confined to the gastrointestinal tract [5].
• Labeled galectin-2 binds to T cells in a beta-galactoside-specific manner [5].
• The carbohydrate-dependent binding of galectin-2 induces apoptosis in activated T cells [5].
• The genomic DNA encoding L-14-II (LGALS2) contains four exons with similar intron placement to L-14-I (LGALS1); but the genomic upstream region, which contains several sequences characteristic of regulatory elements, differs significantly from L-14-I [6].

Biological context of LGALS2

• Two members of the S-lac lectin gene family, LGALS1 and LGALS2, reside in close proximity on human chromosome 22q12-q13 [7].
• Through a case-control study in the Japanese population and subsequent functional analyses, we previously showed that a functional single nucleotide polymorphism (SNP) in the gene encoding galectin-2 (lectin, galactoside-binding, soluble, 2; LGALS2) is associated with susceptibility to myocardial infarction [8].
• Genotype of galectin 2 (LGALS2) is associated with insulin-glucose profile in the British Women's Heart and Health Study [9].
• This clone was shown by DNA sequence analysis to represent the human HL14 gene, encoding a beta-galactoside binding protein, the mouse homologue of which has recently been reported to act as a cell growth inhibitory factor [10].

Anatomical context of LGALS2

• Smooth muscle cells and macrophages in the human atherosclerotic lesions expressed both galectin-2 and LTA [1].

Associations of LGALS2 with chemical compounds

• Here we show that LTA protein binds to galectin-2, a member of the galactose-binding lectin family [1].
• 3) Kinetic analysis of tirilazad hydroxylase activity in three human livers resulted in an apparent Km of 2.12, 1.68 and 1.66 microM, and Vmax = 0.85, 0.44 and 3.45 (nmol/mg protein/min) for HL14, HL17 and HL21, respectively [11].

Other interactions of LGALS2

• This genetic substitution affects the transcriptional level of galectin-2 in vitro, potentially leading to altered secretion of LTA, which would then affect the degree of inflammation; however, its relevance to other populations remains to be clarified [1].

Analytical, diagnostic and therapeutic context of LGALS2

• Human galectin-2: expression profiling by RT-PCR/immunohistochemistry and its introduction as a histochemical tool for ligand localization [12].
• HL-14 could be resolved into at least six acidic forms by isoelectric focusing and HL-29 into at least five acidic forms by this procedure [13].

References