AB 22. Study of IL-1, IL-4 and TNFα polymorphisms in extrinsic and intrinsic asthma in a Greek population
Background: The aim of present study was the definition of the IL-1, IL-4
and TNFα polymorphisms in asthmatic patients and their association with
allergy and bronchial hyperresponsiveness (BHR).
Materials and methods: Thirty patients with allergic asthma, mean
age 35.2±14.51 years (Group A) and 22 patients with non-allergic
asthma, mean age 47.1±16.3 years (Group B) were included in the
study. All patients were recruited from the Asthma Clinic of Pulmonary
Department, University of Thessaloniki. 21 healthy control subjects of
mean age 36.6±10.5 years were also included (Group C). All patients
were subjected to skin prick tests and metacholine challenge. DNA was
extracted from the patients’ peripheral blood samples. Determination of
IL1α -889(T/C), IL1β-511(T/C), IL1β+3962(C/T), IL1R1970(C/
T), IL1RA mspa111100(C/T), IL4-1098(T/G), IL4-590(C/T), IL4-
33(C/T), TNFα-308(G/A) and TNFα-238(G/A) polymorphisms
were performed by PCR using the INVITROGEN kit (C: cytokine, T:
thymine, G: Guanine και A: Adenine).
Results: Analysis of IL-1 polymorphisms and in particular IL-1β
(+3962) showed statistically significant differences between Group
A-B (P=0.029) and Group B-C (P=0.024) respectively. Furthermore,
analysis for IL-1 receptor (IL1R) showed statistically significant
differences between Group B and C, where C/T showed an increased
frequency in Group B and C/C in Group C (P=0.003). Besides, analysis
of IL-1 receptor antagonist (IL-1RA) in C/T and Τ/Τ genotypes
showed increased frequencies in Group A and C respectively (P=0.03).
Analysis of IL4 -1098 polymorphisms showed an increased frequency of
guanine in Group A (P=0.036) when compared to Group C whereas for
IL4-590, C/C genotype showed an increased frequency in Group C and
C/T in Group A (P=0.003), suggesting possible association between
thymine and risk of asthma development. Analysis of TNFα-238 in
G/G and A/G genotypes showed statistically significant differences
between the Group A-C, (P=0.008) and Group B-C (P=0.001). G/G
showed an increased frequency in Group C and A/G in Groups A and
B. Moreover C/T genotype for IL-4 showed positive association with
high concentrations of methacholine (P=0.022) and subsequently low
BHR. On the contrary, G/G genotype in TNFα gene were positively
associated with lower concentrations of methacholine (P: 0.033) and
high BHR.
Conclusions: IL-1, IL-4 and TNFα polymorphisms showed significant differences between patients with allergic and non-allergic asthma and
healthy control subjects, which are possibly associated with risk of
asthma development. BHR was associated with IL-1, IL-4 and TNFα
polymorphisms.