Endocrine Abstracts

Background and aims: High correlation is revealed between type 1 diabetes mellitus (DM1) and autoimmune thyroid pathology in children. Several candidate-genes including CTLA, PTPN, Ins-23Hphl could be associated with the combined autoimmune endocrinopathy. The aim of this study was to define whether polymorphisms of CTLA 49 A/G, PTPN22-1858 C/T, Ins-23Hphl ?/? genes contribute to DM1 and autoimmune thyroiditis (AT) combination development.

Material and methods: Twenty-nine DM1 patients (group 1) and 22 DM1+AT (group 2) with mean age of 9.95 (3.9–16.2) and 14.3 (9.8–16.7) years accordingly were genotyped for our investigation. Mean age at DM1 onset and the disease duration in the 1st group was 9.15 (2.48–14.97) years and 1.1 (0–4); 8.85 (4.93–14.93) and 4.2 (0.56–10.37) (P>0.05) in 2nd group correspondingly. AT criterions: typical ultrasonography signs (in 100%), antibodies to thyroidperoxidase (in 83.4% patients >100 U, in 26.6% – >50<100 U). AT manifestation preceded DM1 in 8.3% of children, started simultaneously in 25% and manifested later in 66.7%. Euthyroidism was observed in 22.7%, subclinic hypothyroidism – in 27.35%, hypothyroidism – in 50% cases. Polymorphism analysis was performed by the PCR method with the specific primers and endonuclease processing of amplificated fragments.

Results: We ascertained PTPN22-1858 T risk-allele high frequency occurrence in DM1 children with the increase of heterozygous carriers (5.7% T/T and 56.6% C/T) in comparison with Belarusian population sample (4.4% T/T and 29.3% C/T, P<0.01). A significant difference in locus Ins-23Hphl genotype rates was discovered in DM1 children: 86% AA, 7% AT, 7% TT and in the population sample: 52.9% AA, 35.2%AT, 10.7%TT (P<0.01). Significant differences between groups 1 and 2 weren’t revealed in connection with latest AT onset.

Conclusion: The increased risk-allele frequency of PTPN22-1858 T and Ins-23Hphl ? genes was observed in Belarusian children with combined autoimmune endocrinopathy.