De-coding genetic risk variants in type 1 diabetes.
Immunol Cell Biol
; 99(5): 496-508, 2021 05.
Article
in En
| MEDLINE
| ID: mdl-33483996
ABSTRACT
The conceptual basis for a genetic predisposition underlying the risk for developing type 1 diabetes (T1D) predates modern human molecular genetics. Over half of the genetic risk has been attributed to the human leukocyte antigen (HLA) class II gene region and to the insulin (INS) gene locus - both thought to confer direction of autoreactivity and tissue specificity. Notwithstanding, questions still remain regarding the functional contributions of a vast array of minor polygenic risk variants scattered throughout the genome that likely influence disease heterogeneity and clinical outcomes. Herein, we summarize the available literature related to the T1D-associated coding variants defined at the time of this review, for the genes PTPN22, IFIH1, SH2B3, CD226, TYK2, FUT2, SIRPG, CTLA4, CTSH and UBASH3A. Data from genotype-selected human cohorts are summarized, and studies from the non-obese diabetic (NOD) mouse are presented to describe the functional impact of these variants in relation to innate and adaptive immunity as well as to ß-cell fragility, with expression profiles in tissues and peripheral blood highlighted. The contribution of each variant to progression through T1D staging, including environmental interactions, are discussed with consideration of how their respective protein products may serve as attractive targets for precision medicine-based therapeutics to prevent or suspend the development of T1D.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Diabetes Mellitus, Type 1
Type of study:
Etiology_studies
/
Risk_factors_studies
Limits:
Animals
Language:
En
Journal:
Immunol Cell Biol
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2021
Type:
Article
Affiliation country:
United States