Associations of genetic polymorphisms of Siglecs with human diseases.

Abstract:

:Genetic polymorphism studies in humans provide unique opportunities to understand human biology and the mechanisms of diseases. Correlations between polymorphisms in the genes encoding human Siglecs and various diseases have been reported. Leading examples, such as the CD33 polymorphism associated with late-onset Alzheimer's disease, are well supported by genetic replication and mechanistic studies, while some others (such as SIGLEC8 polymorphism associated with bronchial asthma and SIGLEC14 polymorphism associated with exacerbation of chronic obstructive pulmonary disease) may benefit reinforcement by independent genetic replication or mechanistic studies. In a few cases, such as MAG polymorphism associated with psychological disorder and CD22 polymorphism associated with autoimmune disease, the phenotype associated with a genetic polymorphism of a Siglec gene and that of an enzyme gene involved in the biosynthesis of Siglec ligand show some overlap, providing indirect support for the observed genotype-phenotype association. Although studies using engineered mutant mice have provided invaluable insights into the biological functions and mechanisms of diseases, it is not always possible to develop appropriate mouse model to replicate human situations because of significant species-to-species differences, which can be a major obstacle in understanding the biology of some of human CD33/Siglec-3-related Siglecs. Further studies in genetic polymorphisms of human Siglecs, combined with appropriate functional studies, may reveal unexpected biological roles of human Siglecs, and identify possible targets for prevention and/or treatment of certain diseases.

journal_name

Glycobiology

journal_title

Glycobiology

authors

Angata T

doi

10.1093/glycob/cwu043

subject

Has Abstract

pub_date

2014-09-01 00:00:00

pages

785-93

issue

9

eissn

0959-6658

issn

1460-2423

pii

cwu043

journal_volume

24

pub_type

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