engleski

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

We investigated potential association of two TNF-α gene promoter SNPs (-238G>A and -308G>A) with type 1 diabetes mellitus (T1DM) incidence in Croatian population and clinical parameters of T1DM Croatian patients. Polymorphisms were analyzed by PCR-RFLP in 174 T1DM patients and 193 healthy controls. Statistical data analysis was performed by SPSS 13 and Arlequin software. 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 than in controls, but only at -308 locus. The distribution of -238G/-308A haploype was also significantly higher in patients compared to controls (27.6% vs 9.6%, p<0.0001). Gender-dependant analysis revealed that female T1DM -308GA genotype carriers exhibit considerably stronger association with T1DM incidence (OR=6.37 ; 95% CI 3.16-12.85) than male -308GA patients (OR=2.71 ; 95% CI 1.31-5.59). Clinical parameter analysis of T1DM patients revealed that -238A allele carriers had significantly decreased level of hemoglobin A1c (HbA1c) compared to G allele carriers at the same position (6.55% vs 7.17%, p=0.022), as well as tendency of risk allele carriers at -238 or -308 locus get T1DM earlier in life compared to non-risk allele carriers. The susceptibility to T1DM in Croatian population is strongly associated with TNF-α -308G>A polymorphism, especially in female. In addition, significantly lower HbA1c level found in T1DM -238A allele carriers might indicate better glycemic control in these patients.

type 1 diabetes ; TNF-α gene ; polymorphism

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