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A common UCP2 polymorphism predisposes to stress hyperglycaemia in severe sepsis

Lookup NU author(s): Dr Angela Pyle, Professor Mark Walker, Professor Patrick Chinnery, Dr Simon Baudouin


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Background: Insulin resistance and hyperglycaemia are common in severe sepsis. Mitochondrial uncoupling protein 2 (UCP2) plays a role in insulin release and sensitivity. Objectives: To determine if a common, functional polymorphism in the UCP2 gene promoter region (the 2866 G/A polymorphism) contributes to the risk of hyperglycaemia in severe sepsis. Results: In the prospective group 120 non-diabetic patients who were carriers of the G allele had significantly higher maximum blood glucose recordings than non-carriers (mean (SD) AA 8.5 (2.2) mmol/l; GA 8.5 (2.4) mmol/l; GG 10.1 (3.1) mmol/l; p=0.0042) and required significantly more insulin to maintain target blood glucose (p=0.0007). In the retrospective study 103 non-diabetic patients showed a similar relationship between maximum glucose and UCP genotype (AA 6.8 (2.3) mmol/l; GA 7.8 (2.2) mmol/l; GG 9.2 (2.9) mmol/l; p=0.0078). Conclusions: A common, functional polymorphism in the promoter region of the UCP2 gene is associated with hyperglycaemia and insulin resistance in severe sepsis. This has implications for our understanding of the genetic pathophysiology of sepsis and is of use in the stratification of patients for more intensive management.

Publication metadata

Author(s): Pyle A, Ibbett IM, Gordon C, Keers SM, Walker M, Chinnery PF, Baudouin SV

Publication type: Article

Publication status: Published

Journal: Journal of Medical Genetics

Year: 2009

Volume: 46

Issue: 11

Pages: 773-775

ISSN (print): 0022-2593

ISSN (electronic): 1468-6244

Publisher: BMJ Group


DOI: 10.1136/jmg.2009.067173


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