NeuroD1 gene and interleukin-18 gene polymorphisms in type 1 diabetes in Dalmatian population of Southern Croatia.

AIM: To evaluate the frequency of known polymorphisms in the exon 2 of the NeuroD1 gene and in the interleukin (IL)-18 promoter region in patients with type 1 diabetes mellitus (T1DM) and in healthy control subjects in Dalmatia, Southern Croatia. METHODS: A total of 134 unrelated patients (73 men and 61 women) and 132 consecutive unrelated healthy controls (61 men and 71 women) from the Dalmatian region of southern Croatia were recruited for the study. NeuroD1 genotypes (GG, GA, AA) were identified by means of polymerase chain reaction followed by restriction fragment length polymorphism (PCR/RFLP). IL-18 polymorphism in the position -137 of the promoter region was detected by using PCR sequence-specific primers. RESULTS: Genotype distributions of both genes did not show significant difference between patients and controls. CONCLUSION: Our results suggest that NeuroD1 exon 2 and IL-18 promoter gene polymorphisms are not associated with development of T1DM susceptibility in the population of South Croatia. In addition to previously published positive correlations of these polymorphisms with development of T1DM among different world populations, our findings indicate the existence of ethnic variations in the association of these genes with disease development.

FokI polymorphism, vitamin D receptor, and interleukin-1 receptor haplotypes are associated with type 1 diabetes in the Dalmatian population.

Vitamin D and interleukin (IL)-1 have been suggested to function in the pathogenesis of type 1 diabetes mellitus (T1DM). Therefore, we examined the influence of gene polymorphisms in vitamin D receptor (VDR) and interleukin-1 receptor type I (IL-1-R1) on susceptibility to T1DM in the Dalmatian population of South Croatia. We genotyped 134 children with T1DM and 132 controls; for FokI polymorphism studies, we extended the control group to an additional 102 patients. The VDR gene polymorphism FokI displayed unequal distribution (P = 0.0049) between T1DM and control groups, with the ff genotype occurring more frequently in T1DM individuals whereas the VDR gene polymorphism Tru9I did not differ in frequency between studied groups. All tested polymorphisms of the IL-1-R1 gene [PstI, HinfI, and AluI (promoter region) and PstI-e (exon 1B region)] displayed no differences between cases and controls. Haplotype analysis of the VDR gene (FokI, BsmI, ApaI, TaqI, Tru9I) and of the IL-1-R1 gene (PstI, HinfI, AluI, PstI-e) found haplotypes VDR FbATu (P = 0.0388) and IL-1-R1 phap' (P = 0.0419) to be more frequent in T1DM patients whereas the BatU haplotype occurred more often in controls (P = 0.0064). Our findings indicate that the VDR FokI polymorphism and several VDR and IL-1-R1 haplotypes are associated with susceptibility to T1DM in the Dalmatian population.

Family-based analysis of vitamin D receptor gene polymorphisms and type 1 diabetes in the population of South Croatia.

Type 1 diabetes mellitus (T1DM) is a disease characterised by the autoimmune destruction of insulin-producing pancreatic beta cells. Vitamin D is a known immune system modulator and its effects are exerted via the vitamin D receptor (VDR). Several VDR gene single nucleotide polymorphisms (SNPs) have been commonly studied in relation to T1DM. The aim of this study was to evaluate the role of VDR gene variation in T1DM susceptibility by genotyping four SNPs (FokI-rs10735810, TaqI-rs731236, BsmI-rs1544410, and Tru9I-rs757343) in 160 case-parent trio samples from the population of South Croatia. We observed overtransmission of Tru9I allele G and undertransmission of the Tru9I-BsmI A-A haplotype from parents to affected children (P = 0.032, P = 0.002, respectively). These results indicate a possible role of the VDR gene in T1DM aetiology. In conclusion, this family-based study presents some evidence of association of specific VDR gene variants with T1DM in the population of South Croatia.