@Article{ecn.2010.0215,
AUTHOR = {Mouna Stayoussef, Jihen Benmansour, Fayza A. Al-Jenaidi, Mansoor H. Rajab, Hichem B. Said, Mohamed Ourtani, Chiheb B. Rayana, Touhami Mahjoub, Wassim Y. Almawi},
TITLE = {Identification of specific tumor necrosis factor-α-susceptible and -protective haplotypes associated with the risk of type 1 diabetes},
JOURNAL = {European Cytokine Network},
VOLUME = {21},
YEAR = {2010},
NUMBER = {4},
PAGES = {285--291},
URL = {http://www.techscience.com/ECN/v21n4/65847},
ISSN = {1952-4005},
ABSTRACT = {Aim. We investigated the association of tumor necrosis factor (TNF)α gene polymorphism with
type 1 diabetes (T1D). Methods. TNF-α -1031T/C, -863C/A, -857C/T, -376G/A, -308G/A, -238G/A, and +488G/A
single nucleotide polymorphisms (SNPs) were assessed in 198 T1DM patients and 180 age-and gender-matched,
normoglycemic control subjects using PCR-restriction fragment length polymorphism (RFLP). Results. Higher
frequencies of -863A (p = 8.0 × 10<sup>-6</sup>
), -857T (p = 1.4 × 10<sup>-4</sup>
), and -238A (p = 0.002) alleles were seen in T1D
patients than in the control group. Significant differences were noted in the distribution of -863T/C, -857C/T,
-376G/A, -308G/A, and -238G/A genotypes between patients and controls. Haploview analysis revealed high
linkage disequilibrium (LD) between the -376G/A and -308G/A SNPs, but this was lower between the other
polymorphisms. Five-locus TNFα haplotypes were constructed based on the prevalence of individual SNPs and
the LD between them. An increased frequency of CTGGG, CCGAG, and ACGGG haplotypes, and a reduced
frequency of the CCGGG haplotype was seen in patients. When the Bonferroni correction was applied, differ-ences
were significant for the CTGGG (Pc = 1.4 × 10<sup>-3</sup>
), CCGAG (Pc = 0.023), and ACGGG (Pc = 1.2 × 10<sup>-3</sup>
)
haplotypes which were greater, and the CCGGG haplotype (Pc = 3.8 × 10<sup>-5</sup>
) which was smaller, among T1D
patients, thereby conferring susceptibility to and protection from T1D, respectively. Conclusion. These results
demonstrate that TNF-α polymorphisms, in particular -863C/A, -857C/T, and -238G/A, are significantly asso-ciated
with T1D. Additional studies, on other racial groups, are needed to confirm our findings.},
DOI = {10.1684/ecn.2010.0215}
}