title: 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 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.
authors.affiliation: Ruđer Bošković Institute, Division of Molecular Medicine, Zagreb, Croatia.
authors.forename: Marina
authors.initials: M
authors.lastname: Korolija
authors.forename: Mirko
authors.initials: M
authors.lastname: Hadžija
authors.forename: Edita Pape
authors.initials: EP
authors.lastname: Medvidović
authors.forename: Pajica
authors.initials: P
authors.lastname: Pavkovic
authors.forename: Sanja
authors.initials: S
authors.lastname: Kapitanović
authors.forename: Ivana Pavlić
authors.initials: IP
authors.lastname: Renar
authors.forename: Marijana Popović
authors.initials: MP
authors.lastname: Hadžija
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D017523:Croatia / Q000453:epidemiology; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D014409:Tumor Necrosis Factor-alpha