Kati Ådjers: Genetics of Inflammatory Mediators of Atopy and Asthma in Adults

The prevalence of atopic disorders such as asthma, allergic rhinitis and allergic conjunctivitis in many populations is close to 30%, causing a major burden on the individuals, their health care systems, and on society. The biological bases of these disorders and of atopy in general have undergone investigation to a great extent, but many aspects still need clarification, for example in order to target novel therapies to patients who would benefit.

A total of 1,156 asthma patients and 1,792 non-asthmatic subjects as controls participated in our studies. Allergic rhinitis and conjunctivitis were defined by questionnaire. Of the participants 245 asthma patients and 405 matched control subjects were tested for atopic status by skin prick tests and by measurement of serum IgE levels, and we also determined variety of polymorphisms of candidate genes IL1A, IL4RA, TLR4, IL4, NOS3, and IL13.

The studies demonstrated an epistatic effect on atopy between IL1A and IL4RA genes. Together TLR4 and IL4 showed an epistatic effect on asthma in female subjects. Additionally, an epistatic effect of NOS3 and IL1A influenced degree of atopy. We also showed that allele A of IL13 rs20541 affected the risk for allergic rhinitis and conjunctivitis in asthma patients. In addition, carriers of this allele were predisposed towards multisensitization in asthma.

Our findings suggest that gene-gene interactions affect susceptibility to atopy and asthma as well as severity of atopy in Finnish adults. Even if single nucleotide polymorphisms of candidate genes show no individual effects, two separate polymorphisms can potentiate the effects of each other, predisposing carriers of certain allele combinations to clinical manifestations. Our results indicate that key features of adult atopic asthma phenotype may be high prevalence of the allele A of IL13 rs20541, a multisensitization pattern, and allergic rhinitis and conjunctivitis symptoms.

The dissertation is available online at
http://urn.fi/URN:ISBN:978-952-03-2029-4

The doctoral dissertation of M.D. Kati Ådjers in the field of medicine titled Genetics of Inflammatory Mediators of Atopy and Asthma in Adults will be publicly examined at the Faculty of Medicine and Health Technology of Tampere University at 12 o’clock on Friday 13 August, 2021. The venue is Arvo building Jarmo Visakorpi auditorium, address: Arvo Ylpön katu 34. Professor Johannes Savolainen from the University of Turku will be the opponent while Professor Olli Silvennoinen will act as the custos.

The event can be followed via remote connection.