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

Abstract 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 reac...

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Veröffentlicht in:Human immunology 2010-12, Vol.71 (12), p.1228-1232
Hauptverfasser: Korolija, Marina, Hadžija, Mirko, Medvidović, Edita Pape, Pavkovic, Pajica, Kapitanović, Sanja, Renar, Ivana Pavlić, Hadžija, Marijana Popović
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Sprache:eng
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Zusammenfassung:Abstract 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 A1 c (HbA1 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 HbA1c levels found in T1DM −238A allele carriers might indicate better glycemic control in these patients.
ISSN:0198-8859
1879-1166
DOI:10.1016/j.humimm.2010.09.003