Diabetes
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Diabetes Publish Ahead of Print published online ahead of print December 7, 2007
DOI: 10.2337/db07-0900
This Article
Right arrow Full Text (PDF)
Right arrow Online-Only Appendix
Right arrow All Versions of this Article:
db07-0900v1
57/3/770    most recent
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Aly, T. A.
Right arrow Articles by Eisenbarth, G. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Aly, T. A.
Right arrow Articles by Eisenbarth, G. S.
Related Collections
Right arrowRelated Article
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Original Research

Analysis of SNPs Identifies Major Type 1A Diabetes Locus Telomeric of the MHC

Theresa A. Aly, MD, PhD1,,2, Erin E. Baschal, BA1,,2, Mohamed M. Jahromi, PhD1, Maria S. Fernando, BS1, Sunanda R. Babu, PhD1, Tasha E. Fingerlin, PhD2,,3, Adam Kretowski, MD1,,4, Henry A Erlich, PhD5, Pamela R. Fain, PhD1,,2, Marian J. Rewers, MD, PhD1,,3, and George S. Eisenbarth, MD, PhD1,,2

1Barbara Davis Center for Childhood Diabetes and
2Human Medical Genetics Program, University of Colorado at Denver and Health Sciences Center, Aurora, Colorado 80045 USA
3Department of Preventive Medicine and Biometrics, University of Colorado at Denver and Health Sciences Center, Aurora, CO 80045 USA
4Medical Academy of Bialystok, Poland
5Roche Molecular Systems, Alameda, CA 94710, USA

Objective: HLA-DRB1*03-DQB1*0201/DRB1*04-DQB1*0302 (DR3/4-DQ8) siblings who share both MHC haplotypes identical-by-descent with their proband siblings have a higher risk for type 1A diabetes than DR3/4-DQ8 siblings who do not share both MHC haplotypes identical-by-descent. Our goal was to search for non-DR/DQ MHC genetic determinants that cause the additional risk in the DR3/4-DQ8 siblings who share both MHC haplotypes.

Research Design and Methods: We completed an extensive SNP analysis of the extended MHC in 237 families with type 1A diabetes from the United States and 1,240 families from the Type 1 Diabetes Genetics Consortium.

Results: We found evidence for an association with type 1A diabetes (rs1233478, p=1.6x10–23, allelic odds ratio=2.0) in the UBD/MAS1L region, telomeric of the classic MHC. We also observed over 99% conservation for up to 9 million nucleotides between chromosomes containing a common haplotype with the HLA-DRB1*03, HLA-B*08, and HLA-A*01 alleles, termed the "8.1 haplotype." The diabetes association in the UBD/MAS1L region remained significant both after chromosomes with the 8.1 haplotype were removed (rs1233478, p1.4x10–12), and after adjustment for known HLA risk factors HLA-DRB1, HLA-DQB1, HLA-B and HLA-A (p=0.01).

Conclusions: Polymorphisms in the region of the UBD/MAS1L genes are associated with type 1A diabetes independent of HLA class II and I alleles.

Correspondence: George.Eisenbarth{at}UCHSC.edu


Add to CiteULike CiteULike   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?

Related Article:

HLA on Chromosome 6: The Story Gets Longer and Longer
Leslie J. Raffel, Janelle A. Noble, and Jerome I. Rotter
Diabetes 2008 57: 527-528. [Extract] [Full Text] [PDF]





HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2007 by the American Diabetes Association.