POLYMORPHISM OF THE BETA CHAIN OF THE HIGH AFFINITY IMMUNOGLOBULIN E RECEPTOR (FcRI-) IN SOUTH AFRICAN BLACK AND WHITE ASTHMATIC AND NONASTHMATIC INDIVIDUALS

To the Editor:

Green and coworkers reported a significant association between the E237G polymorphism of the gene for the  chain of the high affinity receptor for IgE (FcRI-) and asthma bronchiale in a black and white population in South Africa (1). They suggest that polymorphism I181L in FcRI- is a factor that could be used to assign genetic risk of atopy. Other groups had earlier suggested that the Gly237 variant of this polymorphism might be associated with atopy in the Australian and Japanese populations (2, 3), but this variant was of very low frequency in an Italian population (4). The functional significance of this coding polymorphism, which represents an adenine to guanine substitution changing amino acid residue 237 from glutamic acid to glycin in the cytoplasmatic tail of the protein, is not yet known. This change may alter the intracelular signalling capacity of FcRI through the interaction of the protein tyrosine kinase Lyn with the ITAM (immunoreceptor tyrosine activation motif) of the beta chain.

To assess whether these findings are reproducible in other populations, we re-evaluated the relation between this variant and atopic disorders in the Czech population as a part of a study examining the relation between selected polymorphisms of "candidate" genes and atopic predisposition (5).

PCR primers and other conditions used were the same as described elsewhere (3). PCR products were electrophoresed after digestion with XmnI. Serum and DNA were obtained from 157 atopic patients and 77 controls. The atopic patients were selected according to the usually used criteria for atopy (5) and according to clinical diagnosis of some atopic diseases (asthma bronchiale, allergic rhinitis, atopic dermatitis, or their combination). All control subjects showed no personal history of atopy and were taking no related medication.

Genotype Glu237/Gly237 has been found only in one atopic patient with allergic rhinitis, and has been absent in control subjects in our study. It seems, therefore, that the E237G polymorphism neither contributes to the genetic risk of atopic predisposition in the Czech population, nor in the Italian population.

LYDIE HOLLÁ

VIERA KUNROVÁ

SVATAVA TSCHÖPLOVÁ

MARCEL SCHÜLLER

MARCEL STELCL

ANNA VAK

Institute of Pathological Physiology

Medical Faculty

Masaryk University

Brno, Czechoslovakia

1. Green, S. L., M. C. Gaillard, E. Song, J. B. Dewar, and A. Halkas. 1998. Polymorphism of the beta chain of the high-affinity immunoglobulin E receptor (Fcepsilon RI-beta) in South African black and white asthmatic and nonasthmatic individuals. Am. J. Respir. Crit. Care Med. 158 (Pt. 1):1487-1492.

2. Hill, M. R., and W. O. C. M. Cookson. 1996. A new variant of the bcta subunit of the high-affinity receptor for immunoglobulin E (Fcepsilon RI-beta E237G): associations with measures of atopy and bronchial hyperresponsiveness. Hum. Mol. Genet. 5: 959-962 [Abstract/Free Full Text].

3. Shirakawa, T., X. Q. Mao, S. Sasaki, T. Enomoto, M. Kawai, K. Morimoto, and J. Hopkin. 1996. Association between atopic asthma and a coding variant of FcRI in a Japanese population. Hum. Mol. Genet. 5: 1129-1130 [Abstract/Free Full Text].

4. Trabetti, E., V. Cusin, G. Malerba, L. C. Martinati, A. Casartelli, A. L. Boner, and P. F. Pignatti. 1998. Association of the FcepsilonRIbeta gene with bronchial hyperresponsiveness in an Italian population. J. Med. Genet. 35: 680-681 [Abstract/Free Full Text].

5. Hollá, L., A. Vak, V. Znojil, L.  i ková, and J. Vácha. 1999. Association of 3 gene polymorphisms with atopic diseases. J. Allerg. Clin. Immunol. 103:702-708.

From the Authors:

The authors have misinterpreted our results and conclusions. We found no statistical difference in the frequency of the E237G polymorphism of FcRI- between black asthmatics (20%) and black controls (20%) and although white asthmatics had an increased prevalence of the E237G polymorphism (12%) as compared to white controls (5%), this difference was not statistically significant.

Overall the only statistically significant difference was between blacks (20%) and whites (8.5%) (p = 0.001). This finding might explain the population differences in the severity of asthma in South Africa. In our results and discussion we did not suggest that the E237G polymorphism was linked to atopy in either of the populations.

S. L. GREEN

M. C. GAILLARD

Department of Medicine

University of the Witwatersrand

Johannesberg, South Africa