Allelic variants in the PHTF1-PTPN22, C12orf30 and CD226 regions as candidate susceptibility factors for the type 1 diabetes in the Estonian population

The rs6679677 A (OR = 2.13, 95%CI = 1.48-3.08, p = 0.00001), rs17696736 G (OR = 1.53, 95%CI = 1.14-2.04, p = 0.0046) and rs763361 T (OR = 1.48, 95%CI = 1.11-1.98, p = 0.0084) alleles were associated with risk of type 1 diabetes.The current study supports the rs6679677 (PHTF1-PTPN22), rs17696736 (C12orf30) and rs763361 (CD226) SNPs as susceptibility factors for type 1 diabetes outside the major histocompatibility region (MHC) region. The full study had 80% or above to detect an odds ratio of 1.8 under the assumption of an additive model at type 1 error rate, α = 0.05.The genetic predisposition to type 1 diabetes is strongly linked to MHC region [1] but non - MHC locus associated genes are also considered to predispose in the risk of type 1 diabetes. Evidence strongly supports the insulin gene [2], the CTLA-4 locus [3] and the PTPN22 gene [4] as important candidates outside the MHC region. Meanwhile, the established genetic associations with type 1 diabetes explain roughly half of the genetic risk for type 1 diabetes, indicating that other loci exist. In favor of it, genome wide association studies have recently reported new chromosomal regions and novel candidates in the risk of type 1 diabetes [5,6]. Of note, within the CD226 gene (18q22) the rs763361 SNP was found to be associated with type 1 diabetes [5]. The CD226 gene is expressed on the majority of immune cells including natural killer (NK) cells and T cells mediating their activation and differentiation [7]. Moreover, the rs17696736 and the rs6679677 in the chromosomal regions of 12q24 and 1q13 respectively, were also reported to be associated with type 1 diabetes [8]. In particular, the rs17696736 SNP (C12orf30 gene) is located within a large linkage disequilibrium (LD) block that contains several genes of possible function relevance to type 1 diabetes [8]. The rs6679677 SNP is an intergenic SNP located downstream of the round spermatid basic protein 1 (RSBN1) and in the promoter site of the putative homeodom