Handbook of Genetic Counseling/Allergies and Asthma

Allergies and Asthma

General Information about Asthma and Allergy

• Asthma is "a disease characterized by an increased responsiveness of the trachea and bronchi to various stimuli and manifested by a widespread narrowing of the airways. Hyperreactivity, the single most important component of the disease simply means that the airways of asthmatics will react to much smaller amounts of a number of stimuli to produce a certain increase in airways resistance…"
• About 10% of children have asthma. This is usually as part of a syndrome of atopy, which can include the presence of allergy, asthma, seasonal rhinitis and eczema, and tends to occur in familial clusters.
• Symptoms of hay fever and asthma often occur together, but it is not unusual to have just one or the other
• Atopic dermatitis is more likely to be seen in patients with symptoms of hay fever and/or asthma.
• Asthma and other atopic disorders affect a large percentage of the population
• Atopic conditions are characterized by high immunoglobulin E (IgE) responses to common antigens (environmental allergens)
• The most common allergens, resulting in atopic asthma are: home dust saprophytes, pollens, feather, fungus shreds, animal fur, insect poison, animal sweat, food, drugs and other chemical substances.
• 2001 study found house dust mites and cat produced allergens are the most frequent direct causes of acute airway constriction, occupational environment is responsible in 5 to 10% of cases, and other allergic reactions (such as hay fever) produced about 13%.
• Serum IgE levels and specific IgE antibody levels are used in determining allergic status because there is a significant positive correlation between allergic status and total serum IgE level.
• However there are individuals with high IgE levels who are not clinically allergic and have negative skin tests

Genetics of Atopic Conditions

• Many factors contribute to the phenotype of asthma and it is generally believed to be multifactorial, but there is a strong genetic predisposition and many scientists believe the genetic factors are more responsible than environmental factors
• However the genetic factors responsible may be different in different families (genetic heterogeneity)
• The relationship between genetic inheritance and asthma was shown to be quite strong in a study just published in 2001. Children are 3.2 times more likely to develop asthma than the general population if their mothers had asthma, 2.9 times more likely if their fathers had it, and 7 times more likely if both parents had it
• Twin studies indicate approximately a .6 heritability factor for both total serum IgE levels and bronchial hyperreactivity
• IL-4 is a central mediator of allergic inflammation. Along with IL-13, it is the major cytokine responsible for the induction of IgE synthesis.
• Many other genes have been implicated as playing a role in asthma, but it was too many to really research thoroughly on med-line although I started to and got a little carried away
• The press got hold of the announcement of a newly discovered asthma gene in Feb 2001, that was supposed to account for up to 40% of asthma cases. Many scientists were skeptical about this finding and I couldn't find an actual journal article to tell me anything substantial about it. (I would want to look into this further, but I already spent way too much time on this)
• In 1992 a gene for atopy was assigned to chromosome 11q by linkage to the marker D11S97. These findings show that transmission of atopy at the chromosome 11q locus is detectable only through the maternal line. The pattern of inheritance is consistent either with paternal genomic imprinting or with maternal modification of developing immune responses.
• There also seems to be data to suggest heritability of .47 for the release of mediators like histamine

Genetic Counseling Risk Factors

• The genetics of allergic disease is still not clear, the picture that is being built is very complex, and the actual risks are therefore somewhat uncertain and vary within the literature
• One quote for the empiric risk to a child if one parent was affected was as high as 60%, but a quote from a more current article was 20% for the average risk if one parent is affected
• Two major competing models seem to fit the data in different studies. These are probably highly simplified (see table)
  • Recessive model in which "high IgE allele is recessive" and "low IgE allele" is dominant
  • We can't rule this out from the pedigree. Using this model, risks can be as high as 50% if Mr. R is a carrier for "high IgE allele" (but remember that high IgE is not completely predictive of allergic diease)
• Multifactorial model
  • Would be influenced by the number and disease status of other children they have. However, they don't have any yet
  • Risks don't change as drastically with the birth of one affected child
    • These risks were from a book published in 1992, but it still seems that this is the same debate as of 2000
• Data suggest that a single locus gene explains a portion of asthma that is related to the history of atopic diseases. In addition, a polygenic/multifactorial (genetic and environmental factors) influence with a recessive component inheritance may be involved in the pathogenesis of asthma. Am. J. Med. Genet. 93:373-380, 2000. © 2000 Wiley-Liss, Inc.

Other factors affecting atopic conditions

• Age effects
  • Children increasing likely to become allergic from age 2 - young adulthood
• Sex effects
  • Boys more likely to be allergic as girls (twice as likely under age 10 to get atopic asthma)
  • As adults more women develop allergies and rates are similar
• Racial differences
• Smoking
  • May raise IgE levels slightly

Ways to reduce risks to children

• Several studies have shown that breast-fed babies are less likely to develop allergic disease later in life, but other studies have shown no differences in allergies or mean total serum IgE
• Dust control the home
• Avoid exposures to new allergens (proteins in the workplace and new pets)
• Pregnant and nursing women with high risks for allergies in their fetus should avoid certain foods such as milk, eggs, peanuts, nuts, and chocolate as well as reduce wheat, corn, soy, fish, and citrus products during last trimester
• These same foods should not be given to young infants

References

• The Genetic Basis of Common Disorders. Rotter, J.I, King, R. A., & Motulsky, A.G. Oxford University Press. 1992
• Maternal inheritance of atopic IgE responsiveness on chromosome 11qCookson WO, Young RP, Sandford AJ, Moffatt MF, Shirakawa T, Sharp PA, Faux JA, Julier C, Nakumuura Y and et al. Lancet (1992) 340:381-4
• website Am. J. Med. Genet. 93:373-380, 2000
• website (British Medical Journal, 15/9/01. www.bmj.com)
• Detection of a recessive major gene for high IgE levels acting independently of specific response to allergens. (partial abstract from http://www.healthy.net/library/search/medline.htm ) Author Dizier MH; Hill M; James A; Faux J; Ryan G; le Souef P; Lathrop M; Musk AW; Demenais F; Cookson W
• Address INSERM U155, Paris, France.
• Source Genet Epidemiol, 12(1):93-105 1995
• Regressive logistic modeling of familial aggregation for asthma in 7,934 population-based nuclear families. (partial abstract from http://www.healthy.net/library/search/medline.htm )Author Jenkins MA; Hopper JL; Giles GG .
• Source Genet Epidemiol, 14(3):317-32 1997

Notes

The information in this outline was last updated in 2002.