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Assessment of the role of common genetic variation in the transient neonatal diabetes mellitus (TNDM) region in type 2 diabetes: a comparative genomic and tagging single nucleotide polymorphism approach

Assessment of the role of common genetic variation in the transient neonatal diabetes mellitus (TNDM) region in type 2 diabetes: a comparative genomic and tagging single nucleotide polymorphism approach
Assessment of the role of common genetic variation in the transient neonatal diabetes mellitus (TNDM) region in type 2 diabetes: a comparative genomic and tagging single nucleotide polymorphism approach
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.

0012-1797
2272-2276
Gloyn, Anna L.
e1ef7043-a852-4f6d-ad90-a644e328af88
Mackay, Deborah J.G.
588a653e-9785-4a00-be71-4e547850ee4a
Weedon, Michael N.
4ea46048-ef8b-4052-8ff6-a40cf8f5a913
McCarthy, Mark I.
ff42236d-bc18-406f-898b-d10ce8d0bab2
Walker, Mark
440e66f0-fce4-45cf-a73d-3716f254d87f
Hitman, Graham
30a1c858-bc1d-48e7-b478-613cd580dcda
Knight, Bridget A.
79e17891-238c-4570-bb75-c66f06300753
Owen, Katharine R.
b7373528-92e5-4652-85d4-f29a446b994b
Hattersley, Andrew T.
429254b8-e75b-46bd-a6f6-274130336b0d
Frayling, Timothy M.
ddaaa2c7-b281-4c60-a8d8-8f4657d46974
Gloyn, Anna L.
e1ef7043-a852-4f6d-ad90-a644e328af88
Mackay, Deborah J.G.
588a653e-9785-4a00-be71-4e547850ee4a
Weedon, Michael N.
4ea46048-ef8b-4052-8ff6-a40cf8f5a913
McCarthy, Mark I.
ff42236d-bc18-406f-898b-d10ce8d0bab2
Walker, Mark
440e66f0-fce4-45cf-a73d-3716f254d87f
Hitman, Graham
30a1c858-bc1d-48e7-b478-613cd580dcda
Knight, Bridget A.
79e17891-238c-4570-bb75-c66f06300753
Owen, Katharine R.
b7373528-92e5-4652-85d4-f29a446b994b
Hattersley, Andrew T.
429254b8-e75b-46bd-a6f6-274130336b0d
Frayling, Timothy M.
ddaaa2c7-b281-4c60-a8d8-8f4657d46974

Gloyn, Anna L., Mackay, Deborah J.G., Weedon, Michael N., McCarthy, Mark I., Walker, Mark, Hitman, Graham, Knight, Bridget A., Owen, Katharine R., Hattersley, Andrew T. and Frayling, Timothy M. (2006) Assessment of the role of common genetic variation in the transient neonatal diabetes mellitus (TNDM) region in type 2 diabetes: a comparative genomic and tagging single nucleotide polymorphism approach. Diabetes, 55 (8), 2272-2276. (doi:10.2337/db06-0216).

Record type: Article

Abstract

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.

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Published date: August 2006

Identifiers

Local EPrints ID: 44326
URI: http://eprints.soton.ac.uk/id/eprint/44326
ISSN: 0012-1797
PURE UUID: 0bd096a6-1535-43d4-952a-1296bc472e82
ORCID for Deborah J.G. Mackay: ORCID iD orcid.org/0000-0003-3088-4401

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Date deposited: 26 Feb 2007
Last modified: 17 Dec 2019 01:54

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Contributors

Author: Anna L. Gloyn
Author: Michael N. Weedon
Author: Mark I. McCarthy
Author: Mark Walker
Author: Graham Hitman
Author: Bridget A. Knight
Author: Katharine R. Owen
Author: Andrew T. Hattersley
Author: Timothy M. Frayling

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