METABOLIC GENE POLYMORPHISMS ASSOCIATED WITH ATOPIC BRONCHIAL ASTHMA
Ivaschenko TE1, Sideleva OG1, Zelenina LA2, Antonova EA2, Ostankova JV1, Aseev MV1, Baranov VS1
*Corresponding Author: Professor Dr. Vladislav S. Baranov, Ott’s Institute of Obstetrics/Gynecology, Russian Academy of Medical Sciences, Mendeleevskaya line 3, 199034 St. Petersburg, Russia; Tel/Fax: +07(812) 3280487 E-mail: baranov@vb2475.spb.edu
page: 23

RESULTS

Table 2 shows GST genotype frequencies in healthy controls and ABA children with respect to atopic dermatitis and the age of onset. PCR methods, used in our investigation, allowed us to distinguish the GSTM10/0 and GSTT10/0 subjects from GSTM+/+(+/0) and GSTT1+/+ (+/0) subjects, respectively. Three GSTP1 alleles, GSTP1 *A, GSTP1*B, and GSTP1*C, have been identified by PCR-RFLP, each defined by amino acid changes in two codons 105 (Ile/Val) and 114 (Ala/Val).

Seventy-nine percent of ABA children had a GSTM1 deficiency (0/0) as against 45% of GSTM10/0 genotypes in the control group (p<0.001). The frequency of the GSTM10/0 genotype in the group with late onset of the disease (after the age of 7) was 100%. Especially high levels of homozygous GSTM1 0/0 (90%) were found in ABA patients with atopic dermatitis compared to the ABA children without skin problems (57%) or the controls (45%).

Differences in the distribution of GSTT1 0/0 genotypes were quite obvious in ABA patients (58%) compared to those in the control group (20%) (p<0.001). The frequency of the null genotype in the group of ABA patients with late onset of the disease (after the age of 7) was even more (70%).

The distribution of the GSTP1 genotypes in asthmatic patients and in healthy controls was rather similar: 44 and 53% for GSTP1 A./A, 30 and 25% for GSTP1 A/B, and 23 and 16% for GSTP1 A/C. GSTP1 B/B, GSTP1 B/C, and GSTP1 C/C genotypes were very rare or not found in the control group and in ABA patients (Table 2). Significant differences in the frequency of the GSTP1 A/B genotype, respective to patient age at disease onset, were found. The patients with late asthma onset (after the age of 7) revealed the GSTP1 A/B genotype in 60% of cases, while patients with onset of the disease before 7 years of age, had this genotype in only 21% (p<0.01) of cases.

The results of combined analyses of functionally impaired genotypes of the GST genes are shown in Table 3. The statistical analysis proved a significant preponderance of GSTM1 0/0 and GSTT10/0 genotypes in asthmatic children compared to those in the control group. Almost half of all the asthmatic patients studied could be attributed to both GSTM1 0/0 and GSTT1 0/0 homozygosity, while the proportion of the same double-null homozygotes in the control group was only 12% (<0.001). According to relevant statistical calculations, the presence of both null alleles for GSTM1 and GSTT1 genes increases the risk of asthma disease by more than seven times (OR 7.15; 95% CI = 2.70-18.98).

Another combination of functionally impaired geno­types were also significantly higher in the patients group. Moreover, combination of the GSTM10/0, GSTT10/0, and GSTP1S* genotype was rarely encountered in the control group (8%), while it was a common genotype in the patients group (35%).

 

Table 3. Combined analysis of functionally impaired genotypes of healthy controls and in ABA children with respect to age of onset and atopic dermatitis

 

 

 

 

GSTM10/0
GSTT10/0

 

GSTM10/0
GSTP1S*

 

GSTT10/0
GSTP1S*

GSTM10/0
GSTT10/0
GSTP1S*

Controls

12.0%

28.0%

8.0%

8.0%

ABA patients

49.0%

47.0%

40.0%

35.0%

OR

7.15
2.70-18.98

2.38
0.95-5.38

7.68
2.59-22.79

6.29
2.08-19.08

Onset:
  Before age 7
  After age 7

 

42.0%
70.0%

 

42.0%
60.0%

 

36.0%
50.0%

 

30.0%
50.0%

Atopic dermatitis:
  Yes
  No

 

55.0%
36.0%

 

52.0%
36.0%

 

44.0%
29.0%

 

41.0%
21.0%

GSTP1S* = GSTP1 A/B or GSTP1 A/C or GSTP1 B/C or GSTP1 C/C or GSTP1 B/B.




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