title: Identification of specific tumor necrosis factor-α-susceptible and -protective haplotypes associated with the risk of type 1 diabetes.
abstract: OBJECTIVE
  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 × 10-6), -857T (p = 1.4 × 10-4), 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, differences were significant for the CTGGG (Pc = 1.4 × 10-3), CCGAG (Pc = 0.023), and ACGGG (Pc = 1.2 × 10-3) haplotypes which were greater, and the CCGGG haplotype (Pc = 3.8 × 10-5) which was smaller, among T1D patients, thereby conferring susceptibility to and protection from T1D, respectively.
  
  
  CONCLUSIONS
  These results demonstrate that TNF-α polymorphisms, in particular -863C/A, -857C/T, and -238G/A, are significantly associated with T1D. Additional studies, on other racial groups, are needed to confirm our findings.
authors.affiliation: Research unit of Hematological and Autoimmune Diseases, Faculty of Pharmacy, University of Monastir, Tunisia.
authors.forename: Mouna
authors.initials: M
authors.lastname: Stayoussef
authors.forename: Jihen
authors.initials: J
authors.lastname: Benmansour
authors.forename: Fayza A
authors.initials: FA
authors.lastname: Al-Jenaidi
authors.forename: Mansoor H
authors.initials: MH
authors.lastname: Rajab
authors.forename: Hichem B
authors.initials: HB
authors.lastname: Said
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ourtani
authors.forename: Chiheb B
authors.initials: CB
authors.lastname: Rayana
authors.forename: Touhami
authors.initials: T
authors.lastname: Mahjoub
authors.forename: Wassim Y
authors.initials: WY
authors.lastname: Almawi
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D016555:Matched-Pair Analysis; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D055815:Young Adult
chemical_list: D014409:Tumor Necrosis Factor-alpha