engleski

New candidate gene B4GALNT1 is not associated with type 1 diabetes.

Monosialo-ganglioside (GM2-1) can be found on the pancreatic beta cell membrane. GM2-1 has recently been shown to be target for ICA and GAD autoantibodies associated with type 1 diabetes mellitus (T1DM) development. Beta-1, 4-N acetyl- galactosaminyl transferase 1 (GalNAc-T) is the enzyme involved in the biosynthesis of GM2 gangliosides. GalNAc-T catalyzes the transfer of GalNAc into GM3 by beta-1, 4 linkage resulting in the synthesis of GM2. Enzyme beta-1, 4 GalNAc-T is coded with B4GALNT1 gene located on chromosome 12. The purpose of this study was to examine the relation of B4GALNT1 gene tag single nucleotide polymorphisms (tagSNP) with susceptibility to T1DM. Two analyzed B4GALNT1 tagSNP-s. rs1008314 and rs715930, capture 100% of B4GALNT1 common variation at the r2=0.8, based on the HapMap data. We performed case-control (213 patients and 199 control subjects) and family-based (202 families) studies in Croatian population. Case-control study did not observe an association with T1DM (rs1008314, p=0.3001 ; rs715930, p=0.5256). Also, transmission disequilibrium test did not detect any discrepancy from the expected minor allele transmission (rs1008314, p=0.6547 ; rs715930, p=0.4986) nor for the haplotype transmission from parents to affected child. This is the first ever reported association study to examine B4GALNT1 gene polymorphisms with T1DM. We did not find any evidence to support our hypothesis of B4GALNT1 T1DM association.

Type 1 diabetes; Glicosiltransferase; B4GALNT1;; Ganglioside; Tag polymorphism; association analysis; Croatia

Sažetak je objavljen u časopisu citiranom u Current Contents. 16 (2008) , Suppl. 2