Interaction analysis of the CBLB and CTLA4 genes in type 1 diabetes.
J Leukoc Biol
; 81(3): 581-3, 2007 Mar.
Article
en En
| MEDLINE
| ID: mdl-17209142
ABSTRACT
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.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Antígenos de Diferenciación
/
Antígenos CD
/
Proteínas Adaptadoras Transductoras de Señales
/
Diabetes Mellitus Tipo 1
/
Proteínas Proto-Oncogénicas c-cbl
Tipo de estudio:
Etiology_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
/
Humans
País/Región como asunto:
Europa
Idioma:
En
Revista:
J Leukoc Biol
Año:
2007
Tipo del documento:
Article
País de afiliación:
Reino Unido