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Triplet repeat in the Repin1 3′‐untranslated region on rat chromosome 4 correlates with facets of the metabolic syndrome
Author(s) -
Klöting Nora,
Wilke Barbara,
Klöting Ingrid
Publication year - 2006
Publication title -
diabetes/metabolism research and reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.307
H-Index - 110
eISSN - 1520-7560
pISSN - 1520-7552
DOI - 10.1002/dmrr.713
Subject(s) - biology , quantitative trait locus , genetics , gene , congenic , untranslated region , phenotype , chromosome , microbiology and biotechnology , genotype , rna
Background Congenic and subcongenic rat strains confirmed the quantitative trait loci (QTLs) for facets of the metabolic syndrome between 60.53 and 77.11 Mb on chromosome 4. The analysis of candidate genes in this region favoured the replication initiator 1 ( Repin1 ) characterized by a SNP in the coding region and a triplet repeat (TTT) in the 3′‐untranslated region (3′UTR). Methods We analysed nine rat strains (BB/OK, SHR, F344, BN, DA, LEW, hHTg, WOKW, and their founders WOK‐F) and four wild rats on DNA (sequencing) and RNA level (gene expression in blood, liver, subcutaneous, and epididymal adipocytes). In addition, the rats were phenotypically characterized in order to link the rat phenotype to genotype differences in the QTL on chromosome 4. Results Wild rats were heterozygous for the SNP (C/T), whereas all the inbred strains were homozygous. The shortest triplet repeat was found in SHR (5) and the highest was found in hHTg and WOKW (11), which developed metabolic disorders. The repeat number correlated with most phenotypic traits studied. Using linear multiple regression analysis with repeat size as the dependent variable and considering all the data of this study, it was clearly demonstrated that not only VLDL cholesterol and serum insulin but also the expression of Repin1 in the liver is significantly associated with the repeat size of the 3′UTR. Conclusions It is concluded that the triplet repeat expansion in 3′UTR is involved in metabolic alterations as found in hHTg and WOKW rats and that the functional unknown gene, Repin1 , could be a novel candidate gene for the development of facets of the metabolic syndrome. Copyright © 2006 John Wiley & Sons, Ltd.