title: Genetic polymorphisms and asthma: findings from a case-control study in the Madeira island population.
abstract: BACKGROUND
  Asthma is a complex disease influenced by multiple genetic and environmental factors. While Madeira has the highest prevalence of asthma in Portugal (14.6%), the effect of both genetic and environmental factors in this population has never been assessed. We categorized 98 asthma patients according to the Global Initiative for Asthma (GINA) guidelines, established their sensitization profile, and measured their forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) indexes. Selected single nucleotide polymorphisms (SNPs) were analysed as potential markers for asthma susceptibility and severity in the interleukin 4 (IL4), interleukin 13 (IL13), beta-2-adrenergic receptor (ADRB2), a disintegrin and metalloprotease 33 (ADAM33), gasdermin-like (GSDML) and the signal transducer and activator of transcription 6 (STAT6) genes comparatively to a population reference set.
  
  
  RESULTS
  Although mites are the major source of allergic sensitization, no significant difference was found amongst asthma severity categories. IL4-590*CT/TT and IL4-RP2*253183/183183 were found to predict the risk (2-fold) and severity (3 to 4-fold) of asthma and were associated with a lower FEV1 index. ADRB2-c.16*AG is a risk factor (3.5-fold), while genotype GSDML-236*TT was protective (4-fold) for moderate-severe asthma. ADAM33-V4*C was associated to asthma and mild asthma by the transmission disequilibrium test (TDT). Finally, ADAM33-V4*CC and STAT6-21*TT were associated with higher sensitization (mean wheal size ≥10 mm) to house dust (1.4-fold) and storage mite (7.8-fold).
  
  
  CONCLUSIONS
  In Madeira, IL4-590C/T, IL4-RP2 253/183, GSDML-236C/T and ADAM33-V4C/G SNPs are important risk factors for asthma susceptibility and severity, with implications for asthma healthcare management.
authors.affiliation: Human Genetics Laboratory, University of Madeira, Funchal, 9000-390, Portugal. anabela.berenguer@oulu.fi.|Department of Computer Science and Engineering, University of Oulu, PL 4500, Oulu, 90014, Finland. anabela.berenguer@oulu.fi.
authors.forename: Anabela Gonçalves
authors.initials: AG
authors.lastname: Berenguer
authors.affiliation: Human Genetics Laboratory, University of Madeira, Funchal, 9000-390, Portugal. lgh@uma.pt.
authors.forename: Ana Teresa
authors.initials: AT
authors.lastname: Fernandes
authors.affiliation: Immunoalergology Unit, Dr. Nélio Mendonça Hospital, SESARAM, E.P.E, Funchal, Portugal. migsu@net.sapo.pt.
authors.forename: Susana
authors.initials: S
authors.lastname: Oliveira
authors.affiliation: Unit of Statistics, Dr. Nélio Mendonça Hospital, SESARAM, E.P.E, Funchal, Portugal. mariana@srs.pt.
authors.forename: Mariana
authors.initials: M
authors.lastname: Rodrigues
authors.affiliation: Immunoalergology Unit, Dr. Nélio Mendonça Hospital, SESARAM, E.P.E, Funchal, Portugal. pedro.c.ornelas@mail.telepac.pt.
authors.forename: Pedro
authors.initials: P
authors.lastname: Ornelas
authors.affiliation: Immunoalergology Unit, Dr. Nélio Mendonça Hospital, SESARAM, E.P.E, Funchal, Portugal. diogo.romeira.12@facebook.com.
authors.forename: Diogo
authors.initials: D
authors.lastname: Romeira
authors.affiliation: Immunoalergology Unit, Dr. Nélio Mendonça Hospital, SESARAM, E.P.E, Funchal, Portugal. tserrao1@hotmail.com.
authors.forename: Tânia
authors.initials: T
authors.lastname: Serrão
authors.affiliation: Human Genetics Laboratory, University of Madeira, Funchal, 9000-390, Portugal. arosa@uma.pt.|Medical Sciences Unit, Center of Life Sciences, University of Madeira, Funchal, 9000-390, Portugal. arosa@uma.pt.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Rosa
authors.affiliation: Immunoalergology Unit, Dr. Nélio Mendonça Hospital, SESARAM, E.P.E, Funchal, Portugal. ritacamara@mail.telepac.pt.
authors.forename: Rita
authors.initials: R
authors.lastname: Câmara
mesh_terms: D051722:ADAM Proteins / Q000032:analysis / Q000235:genetics; D000293:Adolescent; D001249:Asthma / Q000235:genetics*; D015415:Biomarkers; D016022:Case-Control Studies; D002648:Child; D019483:Disintegrins / Q000032:analysis / Q000235:genetics; D005260:Female; D005541:Forced Expiratory Volume / Q000235:genetics; D005838:Genotype; D006801:Humans; D018793:Interleukin-13 / Q000032:analysis / Q000235:genetics; D015847:Interleukin-4 / Q000032:analysis / Q000235:genetics; D008297:Male; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011174:Portugal; D018343:Receptors, Adrenergic, beta-2 / Q000032:analysis / Q000235:genetics; D012307:Risk Factors; D050800:STAT6 Transcription Factor / Q000032:analysis / Q000235:genetics; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D014797:Vital Capacity / Q000235:genetics; D000094524:Gasdermins
chemical_list: D051722:ADAM Proteins; D015415:Biomarkers; D019483:Disintegrins; D018793:Interleukin-13; D015847:Interleukin-4; D009363:Neoplasm Proteins; D018343:Receptors, Adrenergic, beta-2; D050800:STAT6 Transcription Factor; C527978:GSDMB protein, human; D000094524:Gasdermins; C450441:ADAM33 protein, human