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Several studies have found a relationship between polymorphisms of the vitamin D receptor gene (VDR) and development of type 1 diabetes (T1DM). The meaning of this observation remains unclear and its relevance must be checked in different population samples. To examine the association of VDR polymorphisms and susceptibility to T1DM in the Dalmatian population of South Croatia we studied 134 individuals with type 1 diabetes and 132 control subjects. VDR genotyping was performed using PCR and BsmI, ApaI and TaqI restriction enzymes. Data were analysed using the χ2-test. The genotype combination which conferred strongest susceptibility to T1DM was BBAAtt (P=0.002). Interestingly, the BAt haplotype was found to be a risk factor in a German population, the only European population tested thus far. Our results indicate that VDR polymorphisms are associated with increased risk of T1DM in the Dalmatian population of South Croatia and warrant further studies. [Copyright &y& Elsevier]

Abstract: Objectives: Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by destruction of pancreatic β cells. Gangliosides are thought to be a target of a variety of anti-islet autoantibodies. The formation of gangliosides is catalyzed by addition of sugar residues to complex glycoconjugate molecules by glycosyltransferases. Beta-1,4-N-acetyl-galactosaminyl transferase 1 is the enzyme involved in the synthesis of asialo, a, b and c-series gangliosides and it is coded by B4GALNT1 gene. Design and methods: We genotyped 2 B4GALNT1 tagSNPs, designed to capture 100% of common variation in the region, in 202 families and 199 controls from the Croatian population. Results: Transmission disequilibrium test and case-control analysis did not detect an association of B4GALNT1 gene with T1DM. Conclusions: Expression of gangliosides requires coordinated work of many genes. There is enough evidence showing that gangliosides are plausible contributors to T1DM pathological processes and, therefore, future studies on different glycosyltransferase genes are necessary. [Copyright &y& Elsevier]

Abstract: Tumor necrosis factor (TNF) and lymphotoxin-α (LTA) are cytokines with a wide range of inflammatory and immunomodulatory activities. Type 1 diabetes is an autoimmune disease characterized by destruction of insulin-producing pancreatic β cells. The aim of the present study was to evaluate the association of polymorphisms in the TNF/LTA gene region with susceptibility to type 1 diabetes. We investigated 11 TNF/LTA tag polymorphisms, designed to capture the majority of common variation in the region, in 160 trio families from South Croatia. We observed overtransmission of alleles from parents to affected child at five variants: (rs909253, allele C, p = 1.2×10−4; rs1041981, allele A, p = 1.1×10−4; rs1800629 (G-308A), allele A, p = 1.2×10−4; rs361525 (G-238A), allele G, p = 8.2×10−3 and rs3093668, allele G, p = 0.014). We also identified overtransmission of the rs1800629(G-308A)-rs361525(G-238A) A-G haplotype, p = 2.384×10−5. The present study found an association of the TNF/LTA gene region with type 1 diabetes. A careful assessment of TNF/LTA variants adjusted for linkage disequilibrium with HLA loci is needed to further clarify the role of these genes in type 1 diabetes susceptibility in the population of South Croatia. [Copyright &y& Elsevier]