Association between LTA, TNF and AGER Polymorphisms and Late Diabetic Complications Export

@article{citeulike:2927983, 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, Ekaterina and Cilio, Corrado and Agardh, Elisabet and Groop, Leif and Agardh, Carl-David}, citeulike-article-id = {2927983}, citeulike-linkout-0 = {http://dx.doi.org/10.1371/journal.pone.0002546}, day = {25}, doi = {10.1371/journal.pone.0002546}, journal = {PLoS ONE}, keywords = {diabetic-complications, genetic-polymorphism, tnf}, month = {June}, number = {6}, pages = {e2546+}, posted-at = {2008-06-26 04:42:12}, priority = {2}, publisher = {Public Library of Science}, title = {Association between LTA, TNF and AGER Polymorphisms and Late Diabetic Complications}, url = {http://dx.doi.org/10.1371/journal.pone.0002546}, volume = {3}, year = {2008} }

TY - JOUR ID - citeulike:2927983 L3 - citeulike-article-id:2927983 N2 - 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. IS - 6 JF - PLoS ONE TI - Association between LTA, TNF and AGER Polymorphisms and Late Diabetic Complications PB - Public Library of Science VL - 3 SP - e2546 KW - diabetic-complications KW - genetic-polymorphism KW - tnf AU - Lindholm, Eero AU - Bakhtadze, Ekaterina AU - Cilio, Corrado AU - Agardh, Elisabet AU - Groop, Leif AU - Agardh, Carl-David PY - 2008/06/25/ UR - http://dx.doi.org/10.1371/journal.pone.0002546 ER -