[The relevance of leukotriene C(4) synthase gene A (-444) C polymorphism to clinical responsiveness to montelukast in patients with asthma].
OBJECTIVE
To investigate the frequency of leukotriene C(4) synthase gene A (LTC(4)S A) -444 C polymorphism in asthmatics of Chinese Han nationality in Southwest China and to evaluate its relevance to clinical responsiveness to leukotriene receptor antagonist.


METHODS
A hundred and fifty asthmatics and 146 healthy blood donors were recruited. The genotype distribution of A/C polymorphism of LTC(4)S A(-444)C gene was analyzed by RELP (restriction fragment length polymorphism). Eighty asthmatics were randomly recruited for a 4 week prospective trial of montelukast and their clinical response to montelukast was evaluated by ACQ and pulmonary function. Urine LTE(4) was detected by ELISA (enzyme linked immunosorbent assay) in asthma patients before and after treatment.


RESULTS
In the 150 asthma patients, the frequencies of A and C alleles at -444 locus of LTC(4)S gene were 83.7% and 16.3%, respectively, and the genotype frequencies of AA and AC/CC were 70.7% and 29.3%, respectively. In the 146 healthy blood donors, the frequencies of A and C alleles at -444 locus of LTC(4)S gene were 87.0% and 13.0%, respectively, and the genotype frequencies of AA and AC/CC were 76.7% and 23.3%, respectively. There was no significant difference in LTC(4)S A(-444)C polymorphism between the asthmatics and the healthy controls (chi(2) = 1.393, 1.301, P = 0.238, 0.25 4, P > 0.05). The asthmatics with the C(-444) allele were younger than the asthmatics with AA with earlier onset age and longer duration of disease compared to those with AA (both P < 0.05). However, there were no significant differences between the two groups in clinical and lung function parameters. Four-week montelukast therapeutic trial demonstrated that asthmatic patients with AC/CC genotype had better response than those with AA genotype and this difference was related to urine LTE(4) level (F = 12.01, P = 0.011).


CONCLUSIONS
In a Southwest Chinese Han population LTC(4)S A(-444)C polymorphism might be a determinant factor in the clinical response of asthma to leukotriene receptor antagonists.
Wu
Yong-Hong
YH
Department of Respiratory Diseases, West China Hospital, Sichuan University, Chengdu 610041, China.
Liu
Chun-Tao
CT
Wang
Ke
K
Geng
Yan-Ming
YM
D000085:Acetates / Q000627:therapeutic use*; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use; D044466:Asian People / Q000235:genetics; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics*; D016022:Case-Control Studies; D003521:Cyclopropanes; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D020024:Leukotriene Antagonists / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011804:Quinolines / Q000627:therapeutic use*; D013440:Sulfides; D016896:Treatment Outcome
D000085:Acetates; D018927:Anti-Asthmatic Agents; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; D005982:Glutathione Transferase; C041116:leukotriene-C4 synthase; C093875:montelukast