Interaction analysis of the CBLB and CTLA4 genes in type 1 diabetes.

Interaction analysis of the CBLB and CTLA4 genes in type 1 diabetes. Research Abstract Details 

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Interaction analysis of the CBLB and CTLA4 genes in type 1 diabetes. Abstract Text:

Felicity Payne,Jason D Cooper,Neil M Walker,Alex C Lam,Luc J Smink,Sarah Nutland,Helen E Stevens,Jayne Hutchings,John A Todd,

Gene-gene interaction analyses have been suggested as a potential strategy to help identify common disease susceptibility genes. Recently, evidence of a statistical interaction between polymorphisms in two negative immunoregulatory genes, CBLB and CTLA4, has been reported in type 1 diabetes (T1D). This study, in 480 Danish families, reported an association between T1D and a synonymous coding SNP in exon 12 of the CBLB gene (rs3772534 G>A; minor allele frequency, MAF=0.24; derived relative risk, RR for G allele=1.78; P=0.046). Furthermore, evidence of a statistical interaction with the known T1D susceptibility-associated CTLA4 polymorphism rs3087243 (laboratory name CT60, G>A) was reported (P<0.0001), such that the CBLB SNP rs3772534 G allele was overtransmitted to offspring with the CTLA4 rs3087243 G/G genotype. We have, therefore, attempted to obtain additional support for this finding in both large family and case-control collections. In a primary analysis, no evidence for an association of the CBLB SNP rs3772534 with disease was found in either sample set (2162 parent-child trios, P=0.33; 3453 cases and 3655 controls, P=0.69). In the case-only statistical interaction analysis between rs3772534 and rs3087243, there was also no support for an effect (1994 T1D affected offspring, and 3215 cases, P=0.92). These data highlight the need for large, well-characterized populations, offering the possibility of obtaining additional support for initial observations owing to the low prior probability of identifying reproducible evidence of gene-gene interactions in the analysis of common disease-associated variants in human populations.

Interaction analysis of the CBLB and CTLA4 genes in type 1 diabetes. Publishing Authors By Initials

F Payne,JD Cooper,NM Walker,AC Lam,LJ Smink,S Nutland,HE Stevens,J Hutchings,JA Todd,

For similar animals: chordata: vertebrates: mammals: rodentia: muridae: murinae: rats research abstracts see: animals: chordata: vertebrates: mammals: rodentia: muridae: murinae: rats research

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Interaction analysis of the CBLB and CTLA4 genes in type 1 diabetes. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of leukocyte biology

VOLUME: 81

Page Numbers: 581-3

Journal Abbreviation: J. Leukoc. Biol.

ISSN: 0741-5400

DAY: 5

MONTH: 01

YEAR: 2007

Interaction analysis of the CBLB and CTLA4 genes in type 1 diabetes. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8405628

Interaction analysis of the CBLB and CTLA4 genes in type 1 diabetes. Keywords Mesh Terms:

KEYWORDS: Rats

MESH TERMS: genetics

Chemical & Substance for Abstract: Interaction analysis of the CBLB and CTLA4 genes in type 1 diabetes. Information

Substance Name: CBLB protein, human

Registry Number: EC 6.3.2.19

Grant and Affiliation Information for Interaction analysis of the CBLB and CTLA4 genes in type 1 diabetes.

AFFILIATION: Juvenile Diabetes Research Foundation/Wellcome Trust, Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/MRC Building, Addenbrooke's Hospital, Cambridge, UK.

Country: United States

AGENCY: United Kingdom Wellcome T

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MEDLINETA: J Leukoc Biol

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