Association of plasma soluble CTLA-4 with lung function and gene polymorphism in Chinese asthmatic children.
BACKGROUND
Cytotoxic T lymphocyte antigen 4 (CTLA-4) is known to downregulate the T(H)2 immune response. Recent studies have suggested an association of CTLA-4 polymorphisms with allergic diseases. We investigated the effects of single nucleotide polymorphisms (SNPs) of CTLA-4 on asthma traits and plasma sCTLA-4 in 298 Chinese asthmatic children and 175 controls.


METHODS
Plasma sCTLA-4, total and allergen-specific IgE concentrations were measured by enzyme immunoassay. Six SNPs, namely -1147CT, +49AG, CT60, JO31, JO30 and JO27_1, in CTLA-4 were genotyped by restriction fragment length polymorphism.


RESULTS
Plasma sCTLA-4 was negatively associated with FEV(1)/FVC (r = -0.146, p = 0.036) among our asthmatic patients. Analysis of locus-locus interaction by generalized multifactor dimensionality reduction showed that -1147CT was the best model for plasma sCTLA-4 with a cross-validation consistency of 10 out of 10 and a prediction error of 40.9% (p < 0.001). Multivariate regression analysis confirmed the association between plasma sCTLA-4 concentration with -1147CT among the 6 SNPs tested (p = 0.002) after adjustment for gender and age. The plasma sCTLA-4 concentration was significantly lower in patients homozygous for the C allele than in T allele carriers (p = 0.001). There was also a significant association between the most common haplotypes with low sCTLA-4 in asthmatics. We could not find any significant association between plasma total IgE, atopy and lung function with the 6 SNPs after Bonferroni correction.


CONCLUSIONS
Plasma sCTLA-4 is associated with lung function and -1147CT polymorphism in Chinese asthmatic children. This may help to identify CTLA-4 signaling as a potential therapeutic target in asthma.
Chan
Iris H S
IH
Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, SAR, China.
Tang
Nelson L S
NL
Leung
Ting F
TF
Lam
Yvonne Y O
YY
Wong
Gary W K
GW
Wong
Chun K
CK
Lam
Christopher W K
CW
D000293:Adolescent; D015703:Antigens, CD / Q000097:blood* / Q000235:genetics / Q000276:immunology; D001249:Asthma / Q000097:blood* / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D060908:CTLA-4 Antigen; D002648:Child; D002675:Child, Preschool; D002681:China; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006239:Haplotypes / Q000276:immunology; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D015810:Linkage Disequilibrium / Q000276:immunology; D008168:Lung / Q000503:physiopathology*; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics / Q000276:immunology*; D012129:Respiratory Function Tests; D014797:Vital Capacity / Q000502:physiology
D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D007073:Immunoglobulin E