A common UCP2 polymorphism predisposes to stress hyperglycaemia in severe sepsis.
BACKGROUND
Insulin resistance and hyperglycaemia are common in severe sepsis. Mitochondrial uncoupling protein 2 (UCP2) plays a role in insulin release and sensitivity.


OBJECTIVE
To determine if a common, functional polymorphism in the UCP2 gene promoter region (the -866 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.
Pyle
A
A
Mitochondrial Research Group, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
Ibbett
I M
IM
Gordon
C
C
Keers
S M
SM
Walker
M
M
Chinnery
P F
PF
Baudouin
S V
SV
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D006943:Hyperglycemia / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D007333:Insulin Resistance; D007473:Ion Channels / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011446:Prospective Studies; D012189:Retrospective Studies; D018805:Sepsis / Q000150:complications / Q000235:genetics*; D013312:Stress, Physiological / Q000235:genetics*; D000071246:Uncoupling Protein 2
D001786:Blood Glucose; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604389:UCP2 protein, human; D000071246:Uncoupling Protein 2