Linkage studies for T2D in Chop and C/EBPbeta chromosomal regions in Italians.
The genes causing type 2 diabetes (T2D), a complex heterogeneous disorder, differ and/or overlap in various populations. Among others there are two loci in linkage to T2D, the chromosomes 20q12-13.1 and 12q15. These two regions harbor two genes, C/EBPbeta and CHOP, which are excellent candidate genes for T2D. In fact, C/EBPbeta protein cooperates with HNF4alpha (MODY1, monogenic form of diabetes) and 1alpha (MODY3, monogenic form of diabetes). C/EBPbeta mediates suppression of insulin gene transcription in hyperglycemia and may contribute to insulin-resistance. It interacts in a complex pathway with the CHOP protein. CHOP may play a role in altered beta-cell glucose metabolism, in beta-cell apoptosis, and in lack of beta-cell replication. Thus, both C/EBPbeta and CHOP genes may independently and interactively contribute to T2D. The chromosomal regions targeting C/EBPbeta and CHOP genes have never been previously explored in T2D. We planned to identify their potential contribution to T2D in Italians. We have genotyped a group of affected siblings/families with both late- and early-onset T2D around the C/EBPbeta and the CHOP genes. We have performed non-parametric linkage analysis in the total T2D group, in the late-onset and the early-onset group, separately. We have identified a suggestive linkage to T2D in the CHOP gene locus in the early-onset T2D group (P = 0.04). We identified the linkage to T2D in the chromosome 12q15 region in the early-onset T2D families and specifically target the CHOP gene. Our next step will be the identification of CHOP gene variants, which may contribute to the linkage to T2D in Italians.
Gragnoli
Claudia
C
Laboratory of Molecular Genetics of Monogenic and Complex Disorders, Endocrinology, Diabetes & Metabolism, Medicine and Cellular & Molecular Physiology, Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033, USA. claudia.grapnoli@gmail.com
Pierpaoli
Laura
L
Piumelli
Nunzia
N
Chiaramonte
Francesco
F
D000328:Adult; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism*; D002881:Chromosomes, Human, Pair 12; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism; D005006:Ethnicity / Q000235:genetics*; D005787:Gene Frequency; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D007558:Italy; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism*
D022782:CCAAT-Enhancer-Binding Protein-beta; C497249:DDIT3 protein, human; D051742:Transcription Factor CHOP