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Interaction and association analysis of a type 1 diabetes susceptibility locus on chromosome 5q11-q13 and the 7q32 chromosomal region in Scandinavian families

Holm, P; Rydlander, B; Luthman, Holger LU and Kockum, I (2004) In Diabetes 53(6). p.1584-1591
Abstract
We have previously reported suggestive linkage to chromosome 5p13-q13 in type 1 diabetic families. ISL1, a transcription factor involved in pancreas development, maps to this region. Sequencing of the ISL1 gene in patients and control subjects identified seven single nucleotide polymorphisms (SNPs) and one microsatellite in noncoding regions. Four haplotypes formed by six of these SNPs and one microsatellite were associated with type 1 diabetes in Swedish families (P < 0.04). To identify possible interactions with the 5q11-q13 region, we applied pathway-restricted linkage analysis by analyzing for effects from regions encoding other transcription factors that are active during pancreas development and maintenance of insulin production.... (More)
We have previously reported suggestive linkage to chromosome 5p13-q13 in type 1 diabetic families. ISL1, a transcription factor involved in pancreas development, maps to this region. Sequencing of the ISL1 gene in patients and control subjects identified seven single nucleotide polymorphisms (SNPs) and one microsatellite in noncoding regions. Four haplotypes formed by six of these SNPs and one microsatellite were associated with type 1 diabetes in Swedish families (P < 0.04). To identify possible interactions with the 5q11-q13 region, we applied pathway-restricted linkage analysis by analyzing for effects from regions encoding other transcription factors that are active during pancreas development and maintenance of insulin production. Linkage analysis allowing for interaction between 5q11q13 and 7q32 resulted in an increase of logarithm of odds from 2.2 to 5.3. This increase was estimated to correspond to a P value < 0.0016 using permutation. The transcription factor PAX4 is located at 7q32 and participates downstream of ISL1 in the transcription factor cascade critical to P-cell development. Association with type 1 diabetes was also observed using the transmission disequilibrium test for two haplotypes at the PAX4 locus (P < 0.05). We conclude that pathway-restricted linkage analysis assists in the identification of possible gene-gene interactions and that 5q11-q13 and 7q32 together constitute a significant susceptibility factor for type 1 diabetes. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes
volume
53
issue
6
pages
1584 - 1591
publisher
American Diabetes Association Inc.
external identifiers
  • pmid:15161765
  • wos:000221690200025
  • scopus:2542579529
ISSN
1939-327X
language
English
LU publication?
yes
id
dfb27003-2687-449b-8a9e-5a5d339545a3 (old id 277067)
alternative location
http://diabetes.diabetesjournals.org.ludwig.lub.lu.se/cgi/reprint/53/6/1584
date added to LUP
2007-10-26 16:08:38
date last changed
2017-01-01 07:02:04
@article{dfb27003-2687-449b-8a9e-5a5d339545a3,
  abstract     = {We have previously reported suggestive linkage to chromosome 5p13-q13 in type 1 diabetic families. ISL1, a transcription factor involved in pancreas development, maps to this region. Sequencing of the ISL1 gene in patients and control subjects identified seven single nucleotide polymorphisms (SNPs) and one microsatellite in noncoding regions. Four haplotypes formed by six of these SNPs and one microsatellite were associated with type 1 diabetes in Swedish families (P &lt; 0.04). To identify possible interactions with the 5q11-q13 region, we applied pathway-restricted linkage analysis by analyzing for effects from regions encoding other transcription factors that are active during pancreas development and maintenance of insulin production. Linkage analysis allowing for interaction between 5q11q13 and 7q32 resulted in an increase of logarithm of odds from 2.2 to 5.3. This increase was estimated to correspond to a P value &lt; 0.0016 using permutation. The transcription factor PAX4 is located at 7q32 and participates downstream of ISL1 in the transcription factor cascade critical to P-cell development. Association with type 1 diabetes was also observed using the transmission disequilibrium test for two haplotypes at the PAX4 locus (P &lt; 0.05). We conclude that pathway-restricted linkage analysis assists in the identification of possible gene-gene interactions and that 5q11-q13 and 7q32 together constitute a significant susceptibility factor for type 1 diabetes.},
  author       = {Holm, P and Rydlander, B and Luthman, Holger and Kockum, I},
  issn         = {1939-327X},
  language     = {eng},
  number       = {6},
  pages        = {1584--1591},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  title        = {Interaction and association analysis of a type 1 diabetes susceptibility locus on chromosome 5q11-q13 and the 7q32 chromosomal region in Scandinavian families},
  volume       = {53},
  year         = {2004},
}