Open Access

ARTICLE

Identification of specific tumor necrosis factor-α-susceptible and -protective haplotypes associated with the risk of type 1 diabetes

Mouna Stayoussef¹, Jihen Benmansour¹, Fayza A. Al-Jenaidi^2,3, Mansoor H. Rajab², Hichem B. Said⁴, Mohamed Ourtani⁵, Chiheb B. Rayana¹, Touhami Mahjoub¹, Wassim Y. Almawi³

1 Research unit of Hematological and Autoimmune Diseases, Faculty of Pharmacy, University of Monastir, Tunisia
2 Department of Pediatrics, Salmaniya Medical Complex, Manama, Bahrain
3 College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain
4 Department of Endocrinology, CHU Farhat Hached, Sousse
5 Hospital of Kairouan, Kairouan, Tunisia

* Corresponding Author: W.Y. Almawi,

European Cytokine Network 2010, 21(4), 285-291. https://doi.org/10.1684/ecn.2010.0215

Accepted 02 April 2010;

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^-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, differ-ences 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. 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.

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