Increased total serum IgE levels in patients with asthma and promoter polymorphisms at CTLA4 and FCER1B.
BACKGROUND
Increasing evidence indicates that total serum IgE levels are largely determined by genetic factors, and we recently established that the -109C/T promoter polymorphism at FCER1B is a genetic factor that affects total serum IgE levels. The gene encoding cytotoxic T lymphocyte antigen 4 (CTLA4) is another candidate factor in high IgE responsiveness, because B7-CD28/CTLA4 interaction can promote the differentiation and development of the T(H)2 lymphocyte subset.


OBJECTIVE
We intended to determine whether CTLA4 is associated with increased levels of total serum IgE or with the development of asthma or atopy.


METHODS
We performed a case-control study involving 339 patients with asthma and 305 healthy control subjects, of whom 226 of the patients with asthma and 219 of the healthy control subjects had previously been genotyped for the -109C/T promoter polymorphism at FCER1B. In the current study, we genotyped 2 polymorphisms in the CTLA4 gene, one involving the promoter (-318C/T) and the other involving exon 1 (+49A/G), in addition to the FCER1B promoter polymorphism.


RESULTS
Patients with asthma who were homozygous for the -318C allele at the CTLA4 promoter region had higher levels of total serum IgE than patients with asthma carrying the -318T allele (P =.00470). The analysis of -318C/T (at CTLA4) and -109C/T (at FCER1B) promoter polymorphisms showed a significant correlation between the combined genotypes and increased levels of total IgE in patients with asthma (P =.000014). In contrast, no correlation between total serum IgE levels and -318C/T or +49A/G genotypes was detected in 305 healthy control subjects. There was no evidence indicating an association between a putative allele for asthma or atopy and alleles at any of the CTLA4 polymorphic loci.


CONCLUSIONS
Our findings suggest that promoter polymorphisms of both CTLA4 and FCER1B are genetic factors that influence total serum IgE levels in patients with asthma. This supports the theory that variance in total serum IgE levels in patients with asthma is determined by mutations in multiple genes, each of which has a relatively small effect on the phenotype.
Hizawa
N
N
First Department of Medicine, School of Medicine, Hokkaido University, Sapporo, Japan.
Yamaguchi
E
E
Jinushi
E
E
Konno
S
S
Kawakami
Y
Y
Nishimura
M
M
D000069594:Abatacept; D000328:Adult; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D001249:Asthma / Q000235:genetics* / Q000276:immunology*; D060908:CTLA-4 Antigen; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics / Q000276:immunology; D018796:Immunoconjugates; D007073:Immunoglobulin E / Q000097:blood*; D008297:Male; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D017455:Receptors, IgE / Q000235:genetics*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D017455:Receptors, IgE; D007073:Immunoglobulin E; D000069594:Abatacept