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A Comprehensive, Statistically Powered Analysis of GAD2 in Type 1 Diabetes
Ist Teil von
Diabetes (New York, N.Y.), 2002-09, Vol.51 (9), p.2866-2870
Ort / Verlag
Alexandria, VA: American Diabetes Association
Erscheinungsjahr
2002
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
A Comprehensive, Statistically Powered Analysis of GAD2 in Type 1 Diabetes
Gillian C.L. Johnson 1 ,
Felicity Payne 1 ,
Sarah Nutland 1 ,
Helen Stevens 1 ,
Eva Tuomilehto-Wolf 2 ,
Jaakko Tuomilehto 2 and
John A. Todd 1
1 Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical
Research, University of Cambridge, Cambridge, U.K.
2 Diabetes and Genetic Epidemiology Unit, National Public Health Institute, Helsinki, Finland
Abstract
GAD2 maps to chromosome 10p11.23 and encodes the 65-kDa isoform of GAD65, a major autoantigen in type 1 diabetes. The genetic
variation that influences expression of preproinsulin mRNA, encoding another major autoantigen in type 1 diabetes, has already
been shown to be genetically associated with disease. Previous reports that have assessed the association of GAD2 with type 1 diabetes have not used a dense map of markers surrounding the gene and have relied on very small clinical sample
sizes. Consequently, no definite conclusions can be drawn from their negative results. We have therefore systematically searched
all exons, the 3′ untranslated region (UTR), the 5′ UTR, and the 5′ upstream region of GAD2 , for polymorphisms in 32 white European individuals. We have genotyped these polymorphisms in a maximum of 472 U.K. type
1 diabetic affected sib pair families exhibiting linkage to type 1 diabetes on chromosome 10p and have tested both single
variants and haplotypes in the GAD2 region for association with disease. We subsequently followed up our results by genotyping a subset of these single-nucleotide
polymorphisms in a maximum of 873 Finnish families with at least one affected child. Our results suggest that GAD2 does not play a major role in type 1 diabetes in these two European populations.
Footnotes
Address correspondence and reprint requests to John A. Todd, JDRF/WT Diabetes and Inflammation Laboratory, Cambridge Institute
for Medical Research, Wellcome Trust/MRC Building, Hills Road, Cambridge CB2 2XY, U.K. E-mail: john.todd{at}cimr.cam.ac.uk .
Received for publication 2 April 2002 and accepted in revised form 21 May 2002.
LD, linkage disequilibrium; SNP, single-nucleotide polymorphism; TDT, transmission-disequilibrium test; UTR, untranslated
region.
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