141-P: IMPACT OF HLA-G EXON 8- INDEL POLYMORPHISM AND SOLUBLE LEVELS ON TYPE 1 DIABETES

Abstract

Aim Type 1 Diabetes (T1D) association with HLA-DRB1∗03 /∗04 is reported worldwide, however not all DR3 or DR4 haplotypes predispose equally. HLA-G, a nonclassical class I molecule having immunomodulatory potential is implicated in the pathogenesis of autoimmune diseases, infections, cancers and transplantation. A 14bp INDEL in the 3’-UTR of the HLA-G exon 8 influences the mRNA stability and soluble HLA-G (sHLA-G) levels. Studies on Psoriasis, SLE and RA reported differential ability of 14bp genotypes to counteract inflammation and a potential role of sHLA-G was suggested. Induction of HLA-G expression on dendritic cells from diabetic subjects mediated the inhibition of autologous T cell activation, indicating role in diabetes pathogenesis. Conditional analysis among 2400 T1D affected families, revealed novel association around the HLA-G locus. Presently, we aimed to investigate the role of 14bp INDEL polymorphism in T1D patients from North India. Methods 78 T1D cases and 70 ethnically matched healthy controls (HCs) were tested by PCR-SSP /sequencing. Results The +14bp allele (53% vs 47%) and Genotype +/+14 bp (31% vs 20.5%) were observed more frequently in T1D cohort than in HCs. The study cohort was sub grouped on basis of HLA-DRB1∗03 presence or absence. Among the DR3+ve group, the 14bp +/+ genotype was more common in patients (28% vs 9%) and 14bp-/- was more frequent in the DR3+ve HCs (55% vs 28%). In the DR3-ve cohort, higher number of T1D cases carried the +/+ genotype (43% vs 22%, P=0.04). The 14bp genotypes may lead to variability in the sHLA-G levels in T1D patients which might modulate the autoreactive T cells. Further, the regulation of HLA-G gene expression is also influenced by the G/C SNP at +3142 (of 3’UTR), a putative miRNA binding site. Conclusions Preliminary findings indicate role of 14bpINDEL polymorphism in diabetes pathogenesis. Investigations on sHLA-G levels and +3142 G/C SNP polymorphism is currently ongoing and results will be correlated with above findings and presented.