[Correlation between polymorphism of IL-4 and IL-10 gene promoter and childhood asthma and their impact upon cytokine expression].

OBJECTIVE

To investigate the correlation between the polymorphism of IL-4 and IL-10 gene promoters and the susceptibility of Chinese children to asthma and to study the impact of such polymorphism upon cytokine production.

METHODS

The data of medical history, pulmonary function, hypersensitive test, and serum IgE were recorded among 168 unrelated Chinese children with asthma aged 5 approximately 15. Four polymorphism sites of IL-4 and IL-10 gen promoter regions were determined by PCR/RFLP. The peripheral blood monocyte (PBMC) was cultured and stimulated by lipopolysacchride (LPS). Then the contents of IL-4 and IL-10 gene promoter regions were determined by ELISA. 53 age-matched children without asthma were used as control.

RESULTS

(1) The allele frequencies of-598 (C/T) site of IL-4 gene promoter was significantly different between Chinese children and children of Caucasian and Afro-American origin (P = 0.01). The allele frequency of -1082 (G/A) site, -819 (C/T) site, and -592 (A/C) site in IL-10 gene promoter was significantly different between Chinese children and their British counterparts (P = 0.01). (2) The serum total IgE level was significantly different among children with different allelic sites in IL-4 and IL-10 gene promoters. A allele in IL-10 - 1082 (G/A) site and T allele in IL-10 - 819 (C/T) site -1082 were associated with elevated total serum IgE (P < 0.01, OR = 3.16; P < 0.05, OR = 1.84). (3) The IL-10 level in the supernatant of PBMC culture of children with homozygous genotypes of -819 TT and ATA/ATA in IL-10 gene promoter after stimulation of LPS was the lowest in comparison with those in the supernatant of PBMC culture of children with other genotypes (all P < 0.05). (4) No correlation was found between -589 (C/T) site in IL-4 gene promoter and asthma. There was no significant difference between the increase of IL-4 level in the supernatant of PBMC culture of children with the two different homozygous genotypes of IL-4 gene promoter.

CONCLUSIONS

(1) There is no significant correlation between the polymorphism sites in IL-4 and IL-10 gene promoters and the susceptibility to asthma among Chinese. (2) The polymorphism of IL-10 gene promoter may be an important candidate gene for severity of asthma. The allele -819T plays an important role in increase of the total serum IgE by reducing the upregulation of IL-10 gene expression.