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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]

Author information

1
Departamento de Nutrición, Salud Pública y Epidemiología Genética, Instituto de Nutrición y Tecnología de los Alimentos, Universidad de Chile, Chile.

Abstract

BACKGROUND:

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.

AIM:

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

MATERIAL AND METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

PMID:
23354631
DOI:
10.4067/S0034-98872012000900002
[Indexed for MEDLINE]
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