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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.

Original publication

DOI

10.2337/db06-0216

Type

Journal article

Journal

Diabetes

Publication Date

08/2006

Volume

55

Pages

2272 - 2276

Keywords

Alleles, Animals, Case-Control Studies, Cell Cycle Proteins, Chromosomes, Human, Pair 6, Diabetes Mellitus, Diabetes Mellitus, Type 2, Epigenesis, Genetic, Family, Gene Expression, Genetic Predisposition to Disease, Genetic Variation, Genotype, Humans, Infant, Newborn, Infant, Newborn, Diseases, Mice, Polymorphism, Single Nucleotide, RNA, Messenger, Transcription Factors, Tumor Suppressor Proteins