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Association between LTA, TNF and AGER polymorphisms and late diabetic complications.

Lindholm, Eero LU ; Bakhtadze, Ekaterine LU ; Cilio, Corrado LU ; Agardh, Elisabet LU ; Groop, Leif LU and Agardh, Carl-David LU (2008) In PLoS ONE 3(6).
Abstract
BACKGROUND: Several candidate genes on the short arm of chromosome 6 including the HLA locus, TNF, LTA and AGER could be associated with late diabetic complications. The aim of our study was therefore to explore whether polymorphisms (TNF -308 G-->A, LTA T60N C-->A and AGER -374 T-->A) in these genes alone or together (as haplotypes) increased the risk for diabetic complications. METHODOLOGY/PRINCIPAL FINDINGS: The studied polymorphisms were genotyped in 742 type 1 and 2957 type 2 diabetic patients as well as in 206 non-diabetic control subjects. The Haploview program was used to analyze putative linkage disequilibrium between studied polymorphisms. The TNF, LTA and AGER polymorphisms were associated with the HLA-DQB1 risk... (More)
BACKGROUND: Several candidate genes on the short arm of chromosome 6 including the HLA locus, TNF, LTA and AGER could be associated with late diabetic complications. The aim of our study was therefore to explore whether polymorphisms (TNF -308 G-->A, LTA T60N C-->A and AGER -374 T-->A) in these genes alone or together (as haplotypes) increased the risk for diabetic complications. METHODOLOGY/PRINCIPAL FINDINGS: The studied polymorphisms were genotyped in 742 type 1 and 2957 type 2 diabetic patients as well as in 206 non-diabetic control subjects. The Haploview program was used to analyze putative linkage disequilibrium between studied polymorphisms. The TNF, LTA and AGER polymorphisms were associated with the HLA-DQB1 risk genotypes. The AGER -374 A allele was more common in type 1 diabetic patients with than without diabetic nephropathy (31.2 vs. 28.4%, p = 0.007). In a logistic regression analysis, the LTA but not the AGER polymorphism was associated with diabetic nephropathy (OR 2.55[1.11-5.86], p = 0.03). The AGER -374 A allele was associated with increased risk of sight threatening retinopathy in type 2 diabetic patients (1.65[1.11-2.45], p = 0.01) and also with increased risk for macrovascular disease in type 1 diabetic patients (OR 2.05[1.19-3.54], p = 0.01), but with decreased risk for macrovascular disease in type 2 diabetic patients (OR 0.66[0.49-0.90], p = 0.009). The TNF A allele was associated with increased risk for macrovascular complications in type 2 (OR 1.53 [1.04-2.25], p = 0.03, but not in type 1 diabetic patients. CONCLUSIONS/SIGNIFICANCE: The association between diabetic complications and LTA, TNF and AGER polymorphisms is complex, with partly different alleles conferring susceptibility in type 1 and type 2 diabetic patients. We can not exclude the possibility that the genes are part of a large haplotype block that also includes HLA-DQB1 risk genotypes. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
3
issue
6
article number
e2546
publisher
Public Library of Science (PLoS)
external identifiers
  • wos:000263288000049
  • pmid:18575614
  • scopus:49649128152
ISSN
1932-6203
DOI
10.1371/journal.pone.0002546
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Pediatrics/Urology/Gynecology/Endocrinology (013240400), Unit for Clinical Vascular Disease Research (013242410), Diabetes and Endocrinology (013241530), Unit on Vascular Diabetic Complications (013241510), Cellular Autoimmunity Unit (013241520)
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7fa7d411-2eee-45d8-818f-29c1e6cb639d (old id 1168484)
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http://www.ncbi.nlm.nih.gov/pubmed/18575614?dopt=Abstract
date added to LUP
2016-04-04 09:31:01
date last changed
2024-01-12 14:36:21
@article{7fa7d411-2eee-45d8-818f-29c1e6cb639d,
  abstract     = {{BACKGROUND: Several candidate genes on the short arm of chromosome 6 including the HLA locus, TNF, LTA and AGER could be associated with late diabetic complications. The aim of our study was therefore to explore whether polymorphisms (TNF -308 G-->A, LTA T60N C-->A and AGER -374 T-->A) in these genes alone or together (as haplotypes) increased the risk for diabetic complications. METHODOLOGY/PRINCIPAL FINDINGS: The studied polymorphisms were genotyped in 742 type 1 and 2957 type 2 diabetic patients as well as in 206 non-diabetic control subjects. The Haploview program was used to analyze putative linkage disequilibrium between studied polymorphisms. The TNF, LTA and AGER polymorphisms were associated with the HLA-DQB1 risk genotypes. The AGER -374 A allele was more common in type 1 diabetic patients with than without diabetic nephropathy (31.2 vs. 28.4%, p = 0.007). In a logistic regression analysis, the LTA but not the AGER polymorphism was associated with diabetic nephropathy (OR 2.55[1.11-5.86], p = 0.03). The AGER -374 A allele was associated with increased risk of sight threatening retinopathy in type 2 diabetic patients (1.65[1.11-2.45], p = 0.01) and also with increased risk for macrovascular disease in type 1 diabetic patients (OR 2.05[1.19-3.54], p = 0.01), but with decreased risk for macrovascular disease in type 2 diabetic patients (OR 0.66[0.49-0.90], p = 0.009). The TNF A allele was associated with increased risk for macrovascular complications in type 2 (OR 1.53 [1.04-2.25], p = 0.03, but not in type 1 diabetic patients. CONCLUSIONS/SIGNIFICANCE: The association between diabetic complications and LTA, TNF and AGER polymorphisms is complex, with partly different alleles conferring susceptibility in type 1 and type 2 diabetic patients. We can not exclude the possibility that the genes are part of a large haplotype block that also includes HLA-DQB1 risk genotypes.}},
  author       = {{Lindholm, Eero and Bakhtadze, Ekaterine and Cilio, Corrado and Agardh, Elisabet and Groop, Leif and Agardh, Carl-David}},
  issn         = {{1932-6203}},
  language     = {{eng}},
  number       = {{6}},
  publisher    = {{Public Library of Science (PLoS)}},
  series       = {{PLoS ONE}},
  title        = {{Association between LTA, TNF and AGER polymorphisms and late diabetic complications.}},
  url          = {{http://dx.doi.org/10.1371/journal.pone.0002546}},
  doi          = {{10.1371/journal.pone.0002546}},
  volume       = {{3}},
  year         = {{2008}},
}