engleski

Exploring the genetic overlap of autoimmune risk loci with T1DM

Knowledge accumulated through genetic research of complex diseases emphasize that these diseases develop as a consequence of cumulative effects of polymorphisms in multiple genes. Many of these susceptibility genes overlap between various autoimmune diseases. The aim of this study was to determine whether four SNPs reported as risk variants in juvenile idiopathic arthritis (VTCN1 gene), sarcoidosis (ANXA11 gene), primary biliary cirrhosis (IL12RB gene) and celiac disease (LPP gene), are associated with susceptibility to type 1 diabetes mellitus (T1DM). We genotyped four SNPs (rs2358817, rs1049550, rs6679356, rs9865818) within VTCN1, ANXA11, IL12RB and LPP genes in 265 T1DM family trios in Croatian population. To test the association we performed transmission disequlibrium test (TDT) in all trios and stratified analysis in different age-of-onset groups. Transmission disequilibrium test did not detect an association of VTCN1, ANXA11, IL12RB and LPP gene polymorphisms with T1DM, but interesting trend in IL12RB2 rs6679356 minor allele C overtransmission in patients below 8 years was observed (p=0.075) and undertransmission in patients above 12 years of T1DM onset (p=0.063). We demonstrated that gene regions associated with several autoimmune diseases are not associated with T1DM. These results exclude investigated SNPs as possible common susceptibility loci between several autoimmune diseases and T1D in our sample set. We observed a trend towards overtransmission and undertransmission of IL12RB2 rs6679356 minor allele C in two groups of patients (below 8 years and above 12 years of T1DM onset, respectively) suggesting that common autoimmune loci might play different roles in disease development within different age groups.

SNP; genotyping; type 1 diabetes; autoimmune loci; TDT

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