[The relevance of leukotriene D4 synthase gene A(-444)C polymorphism to clinical responsiveness of leukotriene receptor antagonist in patients with allergic rhinitis].

OBJECTIVE

To investigate the leukotriene D4 synthase gene A (LTD4S A)-444 C polymorphism in persistent allergic rhinitis (AR) of Chinese Han nationality and to evaluate its relevance to clinical responsiveness of leukotriene receptor antagonist.

METHOD

There were 150 patients [87 males, 63 females, average age (38 +/- 14)] diagnosed with persistent AR in Allergy clinic in our hospital from March 2010 to March 2012; 146 healthy controls (78 males, 68 females, mean age (39 +/- 12)). We detected LT D4SA-444C polymorphism and allele frequencies with Polymerase Chain Reaction (PCR) and-Restriction Fragment Length polymorphism (RELP). The treatment group received monotherapy leukotriene receptor antagonist (montelukast) for 4 weeks. Urinary leukotriene D4 (LTD4) levels were detected by enzyme-linked immunosorbent assay (ELISA) before and after treatment, respectively. We evaluated anti-leukotriene treatment response according to the changement of symptoms, signs PTS and urinary LTD4. We tested correlation between LT D4S gene-444C allele frequency and the treatment response by multivariate analysis of variance.

RESULT

(1) LTD4S gene-444 genotype AA/CC, AC/CC frequency is 70.7% (106/150) and 29.3% (44/150), allele A, C frequencies is 67.3% (101/150) and 32.7% (49/150) in AR group, and LTD4S gene-444 genotype AA/CC, AC/CC frequency is 76.7% (112/146) and 23.3% (34/ 146), allele A, C frequencies is 74.0% (108/146) and 26.0% (38/146) in healthy control group, there is not statistically significant difference between two groups. (2) Among 150 AR patients, compared to patients with AA/CC genotype, the genotype AC/CC patients are younger [average age (35 +/- 9), and (50 +/- 18) respectively, F = 5.891, P < 0.05], with earlier age of onset [(31 +/- 4), and (46 +/- 6) respectively, F = 6.985, P < 0.05], longer course of disease [(8.7 +/- 2.1), and (3.1 +/- 2.0) respectively, F = 11.43, P < 0.05], higher symptom scores (8.2 +/- 0.2; 4.8 +/- 0.3), higher signs score (7.3 +/- 3.3; 3.4 +/- 5.1), and the difference was statistically significant. (3) After 4 weeks of montelukast treatment in AR patients, treatment response of anti-leukotriene in genotype AC/ CC patients is better than those in AA/CC genotype patients (F = 11.01, P < 0.05), the differences of treatment response between two groups were correlated with LTD4 levels in vivo, clinical symptoms and signs of patients.

CONCLUSION

In a Chinese Han population the LTD4SA-444B polymorphism might be one of the factors in the clinical response to leukotriene receptor antagonists in persistent AR patients.