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Lookup NU author(s): Professor Mark Walker
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Recent evidence supports the strong overlap between genes implicated in monogenic diabetes and susceptibility to type 2 diabetes. Transient neonatal diabetes mellitus (TNDM) is a rare disorder associated with overexpression of genes at a paternally expressed imprinted locus on chromosome 6q24. There are two overlapping genes in this region: the transcription factor zinc finger protein associated with cell cycle control and apoptosis (ZAC also known as PLAGL1) and HYMA1, which encodes an untranslated mRNA. Several type 2 diabetes linkage studies have reported linkage to chromosome 6q22-25. We hypothesized that common genetic variation at this TNDM region influences type 2 diabetes susceptibility. In addition to the coding regions, we used comparative genomic analysis to identify conserved noncoding regions, which were resequenced for single nucleotide polymorphism (SNP) discovery in 47 individuals. Twenty-six SNPs were identified. Fifteen tag SNPs (tSNPs) were successfully genotyped in a large case-control (n = 3,594) and family-based (n = 1,654) study. We did not find any evidence of association or overtransmission of any tSNP to affected offspring or of a parent-of-origin effect. Using a study sufficiently powered to detect odds ratios of <1.2, we conclude that common variation in the TNDM region does not play an important role in the genetic susceptibility to type 2 diabetes. © 2006 by the American Diabetes Association.
Author(s): Gloyn AL, Mackay DJG, Weedon MN, McCarthy MI, Walker M, Hitman G, Knight BA, Owen KR, Hattersley AT, Frayling TM
Publication type: Article
Publication status: Published
Journal: Diabetes
Year: 2006
Volume: 55
Issue: 8
Pages: 2272-2276
ISSN (print): 0012-1797
ISSN (electronic): 1939-327X
Publisher: American Diabetes Association
URL: http://dx.doi.org/10.2337/db06-0216
DOI: 10.2337/db06-0216
PubMed id: 16873690
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