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Interleukin - 10 promoter polymorphisms
at -1082, -819 and -592
Interleukin - 10 is an important immunoregulatory cytokine involved in downregulation of inflammatory response, B lymphocyte maturation and regulation of Th1 / Th2 lymphocyte sets.
The interleukin-10 gene possesses promoter polymorphisms G-1082A, C-819T and C-592A in partial linkage dysequilibrium which affect the transcription of the interleukin-10 gene and the production of interleukin-10 protein, giving rise to the following genotype-phenotype correlations (from 1, 2) :
Most researchly has focused on the G-1082A polymorphism alone, with results as tabulated :
Genotype
(-1082)
| Phenotype
| Frequency (%)
|
| AA
| Low IL-10 production
| 37.5
|
| GA
| Intermediate IL-10 production
| 41.2
|
| GG
| High IL-10 production
| 21.3
|
Refined analysis taking into account also the C-819T and C-592A polymorphisms yielded :
|
Genotype
(-1082, -819, -592A)
| Phenotype
| Frequency (%)
|
| ATA-ATA | Low IL-10 production | 8.8 |
| ACC-ACC | Low IL-10 production | 9.2 |
| ACC-ATA | Low IL-10 production | 19.5 |
| GCC-ACC | Intermediate IL-10 production | 21.3 |
| GCC-ATA | Intermediate IL-10 production | 19.9 |
| GCC-GCC | High IL-10 production | 21.3 |
Clinically, associations have been described with immune response to hepatitis B vaccination and cardiovascular events in dialysis patients (2, 3), survival in critically ill patients (4), severity of pneumonia (5), lactic acidosis after cardiac surgery (6), susceptibility to Epstein-Barr virus - infection (7) and Epstein-Barr virus-associated gastric carcinoma (8).
References
(1) Turner DM et al. An investigation of polymorphism in the interleukin-10 gene promoter. Eur J Immunogenet 1997 Feb;24(1):1-8
(PMID: 9043871)<Abstract>
(2) Girndt M et al. The interleukin-10 promoter genotype determines clinical immune function in hemodialysis patients. Kidney Int 2001 Dec;60(6):2385-91
(PMID: 11737614)<Abstract>
(3) Girndt M et al. Anti-inflammatory interleukin-10 genotype protects dialysis patients from cardiovascular events. Kidney Int 2002 Sep;62(3):949-55
(PMID: 12164877)<Abstract>
(4) Lowe PR et al. Influence of interleukin-10 polymorphisms on interleukin-10 expression and survival in critically ill patients. Crit Care Med 2003 Jan;31(1):34-8
(PMID: 12544990) <Abstract>
(5) Gallagher PM et al. Association of IL-10 polymorphism with severity of illness in community acquired pneumonia. Thorax 2003 Feb;58(2):154-6
(PMID: 12554901)<Abstract>
(6) Ryan T et al. Lactic acidosis after cardiac surgery is associated with polymorphisms in tumor necrosis factor and interleukin 10 genes. Ann Thorac Surg 2002 Jun;73(6):1905-9
(PMID: 12078789)<Abstract>
(7) Helminen ME et al. Susceptibility to primary Epstein-Barr virus infection is associated with interleukin-10 gene promoter polymorphism. J Infect Dis 2001 Sep 15;184(6):777-80
(PMID: 11517440)<Abstract>
(8) Wu MS et al. Tumor necrosis factor-alpha and interleukin-10 promoter polymorphisms in Epstein-Barr virus-associated gastric carcinoma. J Infect Dis 2002 Jan 1;185(1):106-9
(PMID: 11756988)<Abstract>
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