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Annals of the New York Academy of Sciences
Article . 2008 . Peer-reviewed
License: Wiley Online Library User Agreement
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Independent Association of Tumor Necrosis Factor Polymorphism with Type 1 Diabetes Susceptibility

Authors: Hyoung Doo, Shin; Sei Won, Yang; Duk Hee, Kim; Yongsoo, Park;

Independent Association of Tumor Necrosis Factor Polymorphism with Type 1 Diabetes Susceptibility

Abstract

The contribution of SNPs in TNF genes to type 1 diabetes (T1D) is not well established and may be confounded by the linkage disequilibrium within the HLA genes. Seven SNPs in the TNF genes (TNFA and TNFB) were genotyped in a Korean cohort (398 T1D patients and 1422 nondiabetic controls), along with HLA DRB1, DQB1, and MICA (MHC class I chain‐related genes). Among them, three SNPs (TNFB+318, TNFA‐857, and TNFA‐308) and two common TNF haplotypes showed significant association with the risk of T1D (P= 5 × 10−3–10−5). T1D patients were more often heterozygous for the alleles at the TNFB+318 (OR = 1.7, P= 10−3) and TNFA‐308 (OR = 1.7, P < 10−5) than were the controls. Genetic association analyses of the DRB1, DQB1, and MICA alleles with the risk of T1D revealed dramatic associations in several alleles as expected. Independent analyses to discern the genetic effects of TNF polymorphisms on the risk of T1D suggested that these genetic influences might be not totally dependent on the nearby HLA genes. Our results support the hypothesis that two susceptibility loci in the MHC (one in the HLA class II and another in the central MHC region) act epistatically to increase susceptibility to T1D.

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Keywords

Adult, Aged, 80 and over, Adolescent, Chromosome Mapping, Infant, Middle Aged, Polymorphism, Single Nucleotide, Linkage Disequilibrium, Young Adult, Diabetes Mellitus, Type 1, Gene Frequency, HLA Antigens, Child, Preschool, Tumor Necrosis Factors, Humans, Chromosomes, Human, Pair 6, Genetic Predisposition to Disease, Child, Aged, Genome-Wide Association Study

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
14
Average
Average
Top 10%