Allergy-specific Phenome-Wide Association Study for Immunogenes in Turkish Children.
To dissect the role of immunogenetics in allergy and asthma, we performed a phenome-wide association study in 974 Turkish children selected from a cross-sectional study conducted using ISAAC (International Study of Asthma and Allergies in Children) Phase II tools. We investigated 9 loci involved in different immune functions (ADAM33, ADRB2, CD14, IL13, IL4, IL4R, MS4A2, SERPINE1, and TNF) with respect to 116 traits assessed through blood tests, hypertonic saline challenge tests, questionnaires, and skin prick tests. Multiple associations were observed for ADAM33: rs2280090 was associated with reduced MEF240% (i.e., the ratio of Mean Expiratory Flow after 240s of hypertonic saline inhalation with respect to the age- and ancestry-matched reference value) and with an increased risk of allergic bronchitis (p = 1.77*10(-4) and p = 7.94*10(-4), respectively); rs3918396 was associated with wheezing and eczema comorbidity (p = 3.41*10(-4)). IL4 rs2243250 was associated with increased FEV240 (Forced Expiratory Flow Volume after 240s of hypertonic saline inhalation; p = 4.81*10(-4)) and CD14 rs2569190 was associated with asthma diagnosis (p = 1.36*10(-3)). ADAM33 and IL4 appeared to play a role in the processes linked to allergic airway inflammation and lung function. Due to its association with wheezing and eczema comorbidity, ADAM33 may also be involved in the atopic march.
Aksaray University, Faculty of Health Science, Aksaray, Turkey.
Sefayet
S
Karaca
Ankara Child Health and Diseases Hematology Oncology Research Hospital, Pediatric Allergy and Immunology Clinic, Ankara, Turkey.
Ersoy
E
Civelek
Aksaray University, Faculty of Science and Arts, Department of Biology, Aksaray, Turkey.
Mehmet
M
Karaca
Hacettepe University, Faculty of Medicine, Pediatric Allergy and Asthma Unit, Ankara, Turkey.
Umit M
UM
Sahiner
Hacettepe University, Faculty of Medicine, Pediatrics Department, Unit of Metabolism and Institute of Child Health, Ankara, Turkey.
Riza K
RK
Ozgul
Ankara Child Health and Diseases Hematology Oncology Research Hospital, Pediatric Allergy and Immunology Clinic, Ankara, Turkey.
Can N
CN
Kocabas
Department of Psychiatry, Yale University School of Medicine and VA CT Healthcare Center, West Haven, CT, United States.
Renato
R
Polimanti
Hacettepe University, Faculty of Medicine, Pediatric Allergy and Asthma Unit, Ankara, Turkey.
Bülent E
BE
Sekerel
D051722:ADAM Proteins / Q000235:genetics*; D000293:Adolescent; D001249:Asthma / Q000453:epidemiology / Q000235:genetics*; D002648:Child; D003876:Dermatitis, Atopic / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics; D008297:Male; D014421:Turkey / Q000453:epidemiology
C508598:IL4 protein, human; D015847:Interleukin-4; D051722:ADAM Proteins; C450441:ADAM33 protein, human