Association of TGF-beta1, CD14, IL-4, IL-4R and ADAM33 gene polymorphisms with asthma severity in children and adolescents.
OBJECTIVE
To verify the association of transforming growth factor-beta1(TGF-beta1) (C-509T and T869C), CD14 (C-159T), IL-4 (C-590T), IL-4R (ILe50Val) and ADAM33 (S_2) gene polymorphisms with asthma severity in a sample of patients with mild, moderate and severe persistent atopic asthma.


METHODS
A clinical, laboratory, prospective study was performed in patients with persistent atopic asthma, compared to a control group at Hospital Universitário da Universidade Estadual de Campinas between 2006 and 2007. Analysis of the TGF-beta1 T869C gene polymorphism was performed using the technique polymerase chain reaction (PCR) + amplification refractory mutation system (ARMS). TGF-beta1 C-509T, CD14 C-159T, IL-4 C-590T, IL-4Ra ILe50Val, and ADAM33 S2 gene polymorphisms were detected by PCR and restriction enzyme.


RESULTS
This study included 88 patients with persistent atopic asthma (27 mild, 23 moderate and 38 severe) and 202 healthy blood donors. As to T869C polymorphism (TGF-beta1), there was an association between the CC genotype and patients with severe asthma. There was no association in polymorphisms C-509T (TGF-beta1), C-590T (IL-4) and S_2 (ADAM33). When distribution of C-159T polymorphism genotype frequency (CD14) in severe asthma was compared with the control group, there was a significant result with the TT genotype. There was significant association of the Val/Val genotype (IL-4R) with mild asthma.


CONCLUSIONS
Our results indicate that T869C (TGF-beta1), C-159T (CD14) and Val/Val (IL-4R) polymorphisms might be involved in modulation of asthma severity.
de Faria
Isabel C J
IC
Departamento de Genética, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP.
de Faria
Elisangela J
EJ
Toro
Adyléia A D C
AA
Ribeiro
José Dirceu
JD
Bertuzzo
Carmen Silvia
CS
D051722:ADAM Proteins / Q000235:genetics*; D000293:Adolescent; D001249:Asthma / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D016207:Cytokines / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics; D018950:Lipopolysaccharide Receptors / Q000235:genetics; D008297:Male; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011446:Prospective Studies; D011971:Receptors, Immunologic / Q000235:genetics*; D019948:Receptors, Interleukin-4 / Q000235:genetics; D012720:Severity of Illness Index; D053773:Transforming Growth Factor beta1 / Q000235:genetics
D016207:Cytokines; D005819:Genetic Markers; D018950:Lipopolysaccharide Receptors; D011971:Receptors, Immunologic; D019948:Receptors, Interleukin-4; D053773:Transforming Growth Factor beta1; D015847:Interleukin-4; D051722:ADAM Proteins; C450441:ADAM33 protein, human