TY - JOUR
T1 - Family-based analysis of tumor necrosis factor and lymphotoxin-α tag polymorphisms with type 1 diabetes in the population of South Croatia
AU - Boraska, Vesna
AU - Zeggini, Eleftheria
AU - Groves, Christopher J.
AU - Rayner, Nigel W.
AU - Škrabić, Veselin
AU - Diakite, Mahamadou
AU - Rockett, Kirk A.
AU - Kwiatkowski, Dominic
AU - McCarthy, Mark I.
AU - Zemunik, Tatijana
N1 - Funding Information:
The project is funded by the Croatian Ministry of Science, Education and Sports (number 216-1080315-0293). We thank The British Scholarship Trust for support for the VB study visit to Oxford. EZ is a Wellcome Trust Research Career Development Fellow.
PY - 2009/3
Y1 - 2009/3
N2 - Tumor necrosis factor (TNF) and lymphotoxin-α (LTA) are cytokines with a wide range of inflammatory and immunomodulatory activities. Type 1 diabetes is an autoimmune disease characterized by destruction of insulin-producing pancreatic β cells. The aim of the present study was to evaluate the association of polymorphisms in the TNF/LTA gene region with susceptibility to type 1 diabetes. We investigated 11 TNF/LTA tag polymorphisms, designed to capture the majority of common variation in the region, in 160 trio families from South Croatia. We observed overtransmission of alleles from parents to affected child at five variants: (rs909253, allele C, p = 1.2×10-4; rs1041981, allele A, p = 1.1×10-4; rs1800629 (G-308A), allele A, p = 1.2×10-4; rs361525 (G-238A), allele G, p = 8.2×10-3 and rs3093668, allele G, p = 0.014). We also identified overtransmission of the rs1800629(G-308A)-rs361525(G-238A) A-G haplotype, p = 2.384×10-5. The present study found an association of the TNF/LTA gene region with type 1 diabetes. A careful assessment of TNF/LTA variants adjusted for linkage disequilibrium with HLA loci is needed to further clarify the role of these genes in type 1 diabetes susceptibility in the population of South Croatia.
AB - Tumor necrosis factor (TNF) and lymphotoxin-α (LTA) are cytokines with a wide range of inflammatory and immunomodulatory activities. Type 1 diabetes is an autoimmune disease characterized by destruction of insulin-producing pancreatic β cells. The aim of the present study was to evaluate the association of polymorphisms in the TNF/LTA gene region with susceptibility to type 1 diabetes. We investigated 11 TNF/LTA tag polymorphisms, designed to capture the majority of common variation in the region, in 160 trio families from South Croatia. We observed overtransmission of alleles from parents to affected child at five variants: (rs909253, allele C, p = 1.2×10-4; rs1041981, allele A, p = 1.1×10-4; rs1800629 (G-308A), allele A, p = 1.2×10-4; rs361525 (G-238A), allele G, p = 8.2×10-3 and rs3093668, allele G, p = 0.014). We also identified overtransmission of the rs1800629(G-308A)-rs361525(G-238A) A-G haplotype, p = 2.384×10-5. The present study found an association of the TNF/LTA gene region with type 1 diabetes. A careful assessment of TNF/LTA variants adjusted for linkage disequilibrium with HLA loci is needed to further clarify the role of these genes in type 1 diabetes susceptibility in the population of South Croatia.
KW - Lymphotoxin alpha
KW - TDT
KW - Tag polymorphism
KW - Tumor necrosis factor
KW - Type 1 diabetes
UR - http://www.scopus.com/inward/record.url?scp=61549087771&partnerID=8YFLogxK
U2 - 10.1016/j.humimm.2008.12.010
DO - 10.1016/j.humimm.2008.12.010
M3 - Article
C2 - 19167443
AN - SCOPUS:61549087771
SN - 0198-8859
VL - 70
SP - 195
EP - 199
JO - Human Immunology
JF - Human Immunology
IS - 3
ER -
