Genetic evaluation of the TNF-α -238G>A and -308G>A promoter polymorphisms in Croatian patients with type I diabetes.

A case-control study was performed to establish a potential association of two TNF-α gene promoter SNPs (-238G>A and -308G>A) with occurrence of type 1 Diabetes mellitus (T1DM) in Croatian population (174 patients and 193 healthy controls). Genotypes (obtained by polymerase chain reaction-restriction fragment length polymorphism), and the clinical parameters of T1DM patients were statistically evaluated by SPSS 13 and Arlequin software, G*Power 3.0.10 program, and calculator for Hardy-Weinberg equilibrium. The frequency of the risk (A) allele, as well as the distribution of high-expression (GA, AA) genotypes were significantly higher (p < 0.0001) in T1DM patients only at locus -308. The distribution of the -238G/-308A haplotype was also significantly higher in patients compared with controls (27.6% vs 9.6%, p < 0.0001). Gender-dependent analysis revealed that female T1DM -308GA genotype carriers exhibit considerably stronger association with T1DM (odds ratio = 6.37, 95% confidence interval = 3.16-12.85) than male -308GA patients (odds ratio = 2.71, 95% confidence interval = 1.31-5.59). Clinical parameter analysis of T1DM patients revealed significantly decreased level of hemoglobin A(1)c (HbA(1)c) in -238A allele carriers compared with -238G allele carriers (6.55% vs 7.17%, p = 0.022), as well as the tendency of the risk allele carriers at -238 or -308 locus to develop T1DM earlier in life compared with non-risk allele carriers. In conclusion, susceptibility to T1DM in the Croatian population is strongly associated with the TNF-α -308G>A polymorphism, especially in women. In addition, significantly lower HbA(1c) levels found in T1DM -238A allele carriers might indicate better glycemic control in these patients.
(Copyright © 2010 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)