CTLA-4 Gene Polymorphism in Pediatric Type 1 Diabetes Mellitus: A Case-Control Study

To analyze the relationship between CTLA-4 (+49A/G) polymorphism and pediatric type 1 diabetes mellitus (T1DM).

The observational case-control study was done for 18 months in 44 children (1-16 years of age), 22 of whom had T1DM and 22 controls, were included. CTLA-4 (+49A/G) gene polymorphism was analyzed using polymerase chain reaction-restriction fragment length polymorphism and validated by Sanger sequencing. Various clinical, anthropometric, and biochemistry variables were documented.

The cases and controls were similar in terms of age, gender distribution, family history of diabetes, and consanguinity. The average hemoglobin A1c values were higher in case groups compared to controls (12.41% ±3.09% vs. 4.21 ± 0.5%; P < 0.001). The CTLA4 (+49A/G) gene showed higher frequencies of the G/G genotype in cases compared to controls (54.55% vs. 22.73%; P = 0.030), whereas A/A was found to be higher in controls (P = 0.014). The frequency of the G allele in cases (0.66) was higher than in controls (0.32). The G/G genotype showed higher prevalence in the case group at a younger age, and siblings of offspring showed clustering of the G/G genotype.

In particular, the G/G genotype of the CTLA-4 + 49A/G polymorphism was found to be significantly associated with T1DM in children and to influence the age of onset.