Faculty Collaboration Database

Genetic association of HLA DQB1 with CD4+CD25+(high) T-cell apoptosis in type 1 diabetes. Genes Immun 2009 Jun;10(4):334-40

Date

03/20/2009

Pubmed ID

19295543

DOI

10.1038/gene.2009.14

Scopus ID

2-s2.0-67349143066 (requires institutional sign-in at Scopus site)   19 Citations

Abstract

Type 1 diabetes (T1D) has a strong genetic component and the major locus lies in the HLA DQB1 region. We found earlier an increased apoptosis with decreased viability and function of the CD4+CD25+(high) T-cell subset (Treg) in human subjects with recent-onset T1D and in multiple autoantibody-positive, high at-risk individuals. Tregs normally inhibit or delay onset of T1D in animal models and increased Treg apoptosis could bring on or accelerate disease from effector T-cell-mediated destruction of insulin-producing beta cells. In this study, we test the hypothesis that HLA DQB1 genotypes are associated with increased CD4+CD25+(high) T-cell apoptosis. HLA DQ-based genetic risk status was significantly associated with CD4+CD25+(high) T-cell apoptosis, after adjustment for age, gender and phenotypic status (n=83, F=4.04 (d.f.=3), P=0.01). Unaffected, autoantibody-negative high risk HLA DQB1 control subjects showed increased CD4+CD25+(high) apoptosis levels compared with low risk HLA DQB1 control subjects (n=26, P=0.002), confirming that the association precedes disease. The association of specific HLA DQB1 genotypes with Treg apoptosis was also tested, showing significance for HLA DQB1*0302, DQB1*0201 and HLA DQB1*0602 alleles. Our study shows an association of HLA DQB1 genotypes with CD4+CD25+(high) T-cell apoptosis, which implicates CD4+CD25+(high) T-cell apoptosis as a new intermediate trait for T1D.

Author List

Glisic S, Klinker M, Waukau J, Jailwala P, Jana S, Basken J, Wang T, Alemzadeh R, Hagopian W, Ghosh S

Author

Tao Wang PhD Associate Professor in the Institute for Health and Equity department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Alleles
Apoptosis
CD4 Antigens
Child
Diabetes Mellitus, Type 1
Female
Genetic Predisposition to Disease
Genotype
HLA-DQ Antigens
HLA-DQ beta-Chains
Humans
Interleukin-2 Receptor alpha Subunit
Male
Membrane Glycoproteins
T-Lymphocyte Subsets
T-Lymphocytes, Regulatory
Young Adult