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Rev Med Chil. 2012 Sep;140(9):1109-15. doi: 10.4067/S0034-98872012000900002.

[Decreased caspase 3 expression and cytotoxic T lymphocyte antigen-4 polymorphism in Chilean patients with type 1 diabetes].

[Article in Spanish]

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Departamento de Nutrición, Salud Pública y Epidemiología Genética, Instituto de Nutrición y Tecnología de los Alimentos, Universidad de Chile, Chile.



Several polymorphisms of the CTLA4 gene have been associated with autoimmune diseases. The activation of induced cell death is the major event and caspase 3 represents the main protein for the apoptotic machinery, especially in lymphocytes.


To correlate CTLA4 polymorphisms with caspase 3 expression in peripheral blood mononuclear cells (PBMC) simulating in vitro the glucose effect.


CTLA4 polymorphisms were determined by restriction fragment length polymorphisms (RFLPs). PBMC from 21 patients with type 1 diabetes aged 8.5 ± 4.3 years and 21 healthy subjects aged 18.3 ± 1.8 years, were stimulated under normal (5 mM) and toxic (14 mM) glucose conditions to assess its effect on the expression and activity of caspase 3. Relative abundance of caspase 3 mRNA was measured by semi quantitative RT-PCR and its activity, by a colorimetric assay.


When stimulated with 14 mM glucose, PBMC of G allele carriers with type 1 diabetes had significantly lower relative mRNA abundance of caspase 3 (median value = 0.12, range 0.01-0.70 AU) compared with non-carriers (median value = 0.81, range 0.06-1.09 AU). When the incubation was carried out with the lower glucose concentration, a similar profile of caspase 3 activity was observed in diabetic patients carrying G allele (median value = 0.57, range 0.13-1.20 AU) as compared with non-carriers (median value = 0.89, range 0.14-5.50 AU). No significant changes after stimulating with glucose, were observed in PBMCs of the control group.


PBMC of recently diagnosed patients with T1D, carrying the G allele in + 49A/G polymorphisms of CTLA4, have a decreased expression and activity of caspase 3.

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