RGD Reference Report - Association between LTA, TNF and AGER polymorphisms and late diabetic complications. - Rat Genome Database

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

Authors: Lindholm, E  Bakhtadze, E  Cilio, C  Agardh, E  Groop, L  Agardh, CD 
Citation: Lindholm E, etal., PLoS One. 2008 Jun 25;3(6):e2546.
RGD ID: 2313255
Pubmed: PMID:18575614   (View Abstract at PubMed)
PMCID: PMC2429972   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0002546   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
TNFHumandiabetic angiopathy susceptibilityIAGP associated with Diabetes Mellitus more ...RGD 
TnfRatdiabetic angiopathy susceptibilityISOTNF (Homo sapiens)associated with Diabetes Mellitus more ...RGD 
TnfMousediabetic angiopathy susceptibilityISOTNF (Homo sapiens)associated with Diabetes Mellitus more ...RGD 
LTAHumanDiabetic Nephropathies  IAGP DNA:polymorphismRGD 
LtaRatDiabetic Nephropathies  ISOLTA (Homo sapiens)DNA:polymorphismRGD 
LtaMouseDiabetic Nephropathies  ISOLTA (Homo sapiens)DNA:polymorphismRGD 

Objects Annotated

Genes (Rattus norvegicus)
Lta  (lymphotoxin alpha)
Tnf  (tumor necrosis factor)

Genes (Mus musculus)
Lta  (lymphotoxin A)
Tnf  (tumor necrosis factor)

Genes (Homo sapiens)
LTA  (lymphotoxin alpha)
TNF  (tumor necrosis factor)


Additional Information