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Eur Respir J 2001; 17:1236-1238
Copyright ©ERS Journals Ltd 2001

ABO/Secretor genetic complex and susceptibility to asthma in childhood

F. Ronchetti1, M.P. Villa1, R. Ronchetti1, E. Bonci1, L. Latini1, R. Pascone2, N. Bottini3 and F. Gloria-Bottini4

1 Institute of Pediatric Clinic, 2 Child Health, University of Rome "La Sapienza", Rome, 3 Depts of Internal Medicine, Division of Allergology and Clinical Immunology and 4 Biopathology and Imaging Diagnostics, Division of Preventative and Social Paediatrics, University of Rome "Tor Vergata", Rome, Italy

CORRESPONDENCE: F. Gloria-Bottini, Dipartimento di Biopatologia e Diagnostica per Immagini, Università di Tor Vergata, Via della Ricerca Scientifica, Roma, Italy, 00133. Fax: 39 672596028

Keywords: ABO, age pattern, asthma, oligosaccharide structure, Secretor, sex pattern

Received: December 28, 1999
Accepted January 30, 2001


   Abstract
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 Abstract
Subjects and methods
 Results
 Discussion
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A positive association has recently been reported in adult subjects between O/nonSecretor phenotype and asthma. To confirm this association, this study investigated the joint ABO/Secretor phenotype in a cohort of 165 asthmatic children. Three-hundred and sixty-two consecutive newborn infants from the same population were also studied as controls.

The proportion of O/nonSecretor in asthmatic children was higher than in controls, thus confirming the association found in adults. The association was more marked in males than in females. In males, the pattern of association between the joint ABO/Secretor phenotype and asthma is dependent on the age at on-set of symptoms.

Since the oligosaccharide composition of cell membrane and mucosal secretions is controlled by the cooperative interaction of ABO and Secretor genes, and since such composition influences the adhesion of infectious agents, the age pattern could reflect a more general interaction between developmental maturation and oligosaccharide structure concerning their effects on susceptibility to viral and bacterial agents.

The Secretor gene (FUT2) that encodes for a 2-alpha-l-fucosyltransferase and the ABO blood grouping system that encodes for glycosiltransferases, act in concert to build-up oligosaccharide structures in exocrine secretion systems, including the respiratory tract 1, 2, 3.

Specific oligosaccharide epitopes are necessary for recognition of micro-organisms 4. The product of ABO and Secretor genes seems to influence the adhesion of infectious agents, thus having a modulatory effect on viral and bacterial respiratory infection 3, 5.

A combined analysis of ABO blood groups and salivary Secretor phenotypes was recently performed in a cohort of coal miners. Lower lung function and higher prevalence of wheezing and asthma in nonSecretor subjects of blood group O was shown.

The present study analysed the joint phenotype ABO/Secretor in a cohort of asthmatic children in an attempt to confirm the association observed in adult subjects.


   Subjects and methods
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 Subjects and methods
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The sample study is composed of 165 children, 109 males and 56 females, aged 1 month–15 yrs. The patients were observed in the outpatient paediatric pulmonary clinic of the University of Rome "La Sapienza" or were admitted to a ward of the same clinic for acute respiratory episodes. Both subsamples were consecutive.

The criterion for inclusion in the study was a history of two or more episodes of wheezing in the last 6 months, irrespective of the aetiology/pathogenesis of the attack. A consecutive series of 362 newborn infants from the same population of Rome was considered as a control sample.

ABO and Secretor phenotypes were determined according to standard laboratory procedures 6. Differences of ABO and Secretor phenotype distribution between asthmatics and controls, and association between ABO and Secretor phenotypes were evaluated by the Chi-squared test of independence. Differences of the joint ABO/Secretor phenotype among age classes at on-set in asthmatic children and controls were evaluated by the Chi-squared test of independence.


   Results
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Table 1Go shows, for males and females, the joint ABO/Secretor phenotype distribution in asthmatic children and in consecutive healthy newborns from the same population. The ABO phenotype frequencies in asthmatic children do not differ significantly from controls. Conversely, the frequency of Secretor phenotype is significantly lower in asthmatic children than in controls. This difference is significant in males only. In asthmatic children there is also an association between ABO and Secretor phenotype frequencies, again significant only in males.


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  		Table 1— Distribution of joint ABO/Secretor phenotype in asthmatic children and in healthy newborns (controls).

 
Table 2Go shows the proportion of O/nonSecretor phenotype in asthmatic children and in controls. The proportion is higher in asthmatic than in normal children and the difference is much more marked in males than in females.


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  		Table 2— Per cent proportion of O/non secretor phenotype in healthy and asthmatic children.

 
Table 3Go shows the proportions of the joint ABO/Secretor phenotypes grouped in four categories in relation to age at on-set of asthma. Only male subjects have been considered in this analysis. In relation to age at on-set of clinical manifestations, children were grouped into three categories: 1) on-set in the first year; 2) on-set between 2 and 5 yrs and; 3) on-set after 5 yrs. However, since the last group only includes nine subjects, it has not been considered for all statistical analyses. The distribution of the joint ABO/Secretor phenotypes differs not only between asthmatic and normal children, but also within the asthmatic group.

Table 4Go shows the relative risk values of joint ABO/Secretor phenotypes in asthmatic children belonging to on-set age groups 1) and 2). O/nonSecretor children have a high value of relative risk in both groups, while non-O/Secretor children show a relative risk very near to 1, suggesting a neutral behaviour. The other two joint phenotypes show significant differences concerning the relative risk. Thus, non-O/nonSecretors seem to be more susceptible to asthma in the first year of life and protected in the following years, while O/Secretor individuals seem to be protected against asthma in the first year of life and neutral in following years.


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  		Table 3— Distribution of joint ABO/secretor phenotypes in relation to age at onset of asthma in male children.

 

   Discussion
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 Abstract
 Subjects and methods
 Results
 Discussion
References
 
Alpha-2-fucosyltransferases FUT1 (previously termed H) of red cells and vascular endothelium, and FUT2 (previously termed Se) of exocrine secretion system, are structural genes that collaborate with glycosiltransferases. Glycosiltransferases are controlled by the ABO system, to build oligosaccharide structures on the cell surface of erythrocytes and vascular endothelium, as well as in the exocrine secretion system including the respiratory tract 3.

Previous studies based on separate analysis of the ABO and Secretor systems have led to discordant results 3, 7, 8, 9, probably because of the complexity of the epistatic interactions between these genes. A combined analysis of ABO blood groups and Secretor phenotypes has recently shown, in a cohort of coal miners, a cooperative interaction between the two systems. Blood group O/nonSecretor subjects had lower lung function values and higher prevalence of asthma and wheezing 3. The present data confirm this cooperative interaction concerning susceptibility to asthma in childhood. The association, however, is much more marked in males than in females.

Among the newborn control group, a number of young infants may later develop asthma. In order to evaluate the effects of this bias, a correction factor was introduced under the hypothesis that 10% of newborns will become asthmatic during childhood. With such correction, the differences between asthmatic and (true) controls increase, thus improving the level of significance. For example, in table 1Go, male controls will have a frequency of blood group O nonsecretor equal to 51% (instead of 52.4%) and a frequency of nonSecretor equal to 20.3% (instead of 21.4%).

The analysis of ABO/Secretor types in relation to age at on-set of asthmatic symptoms has revealed an interesting additional pattern of association suggesting that non-O/nonSecretor children are more susceptible in the first year, but not in following years, while the O/Secretor is less susceptible in the first year than in subsequent years. Since at present, it cannot be excluded that the younger age group includes transient wheezers, it is possible that wheezers in the first year include a cluster of subjects well genetically-differentiated from other subjects.

It would be interesting to study the possible relationship of oligosaccharide composition of the cell membrane and of the contiguous secretion layer, with the pattern of common viral and bacterial respiratory infections during the first 5 yrs of life. Susceptibility to classes of micro-organism may depend on interaction between the developmental stage of the individual and oligosaccharide structure of the respiratory mucosa. The association with bronchial asthma could simply be a special aspect of a more general phenomenon.


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  		Table 4— Relative risk of joint ABO/secretor phenotypes in relation to age at onset of asthma.

 

   References
TOP
 Abstract
 Subjects and methods
 Results
 Discussion
 References
 
  1. Oriol R, Le Pendu J, Mollicone R. Genetics of ABO, H, X and related antigens. Vox Sang 1986;51:161–162.[Web of Science][Medline] [Order article via Infotrieve]
  2. Oriol R. ABO Hh, Lewis and secretion. Serology, genetics and tissue distribution In: Cartron JP, Rouger P, editors. Blood Cell Biochemistry, Vol. 6. Molecular Basis of Major Blood Group AntigensNew York, Plenum Press. 1995; pp. 37––73.
  3. Kauffmann F, Frette C, Pham QT, Nafissi S, Bertrand JP, Oriol R. Association of blood group-related antigens to FEV1, wheezing, and asthma. Am J Respir Crit Care Med 1996;153:76–82.[Abstract]
  4. Karlsson KA, Angström J, Bergström J, Lanne B. Microbial interaction with animal cell surface carbohydrates. APMIS 1992;Suppl. 27:71–83.
  5. Raza MW, Blackwell CC, Molyneaux P, et al. Association between secretor status and respiratory viral illness. BMJ 1991;303:815–818.
  6. Boorman KE, Dodd BE. An introduction to blood group serology. 4th Edition, London, Churchill, 1970; pp. 68––74.
  7. Mourant AE, Kopec AC, Domaniewska-Sobczak K. Blood groups and diseases. A study of association of diseases with blood and other polymorphisms Oxford, Oxford University Press, 1978.
  8. Denborough MA, Downing HJ. Secretor status in asthma and hay fever. J Med Genet 1968;5:302–305.[Free Full Text]
  9. Cohen BH, Bias WB, Chase GA, et al. Is ABH non secretor status a risk factor for obstructive lung disease? Am J Epidemiol 1980;111:285–291.[Abstract/Free Full Text]



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