title: T1 and T2 ADAM33 single nucleotide polymorphisms and the risk of childhood asthma in a Saudi Arabian population: a pilot study.
abstract: OBJECTIVE
  Genetic association studies have demonstrated that over 100 variants in target genes (including ADAM33) are associated with airway remodeling and hyper-responsiveness in different ethnic groups; however, this has never been evaluated in Arabic populations. The objective of this study was to determine whether ADAM33 polymorphisms that are associated with asthma in a population of asthmatic children from Saudi Arabia.
  
  
  METHODS
  A cross-sectional pilot study comparing the polymorphisms of normal subjects and asthmatic patients from Saudi Arabia over a period of 1 year.
  
  
  METHODS
  One hundred and seven Saudi asthmatic children and 87 healthy Saudi children of 3-12 years old were assessed for allelic association of ADAM33 T1 (rs2280091), T2 (rs2280090), ST+4 (rs44707) and S1 (rs3918396) SNPs to asthma. Genotyping was done by real-time PCR, multiplex ARMS and PCR-RFLP.
  
  
  RESULTS
  T1 and T2 SNP genotype frequencies in asthmatic children were significantly different compared to controls (P < .05), indicating allelic association with asthma. The T1 A/G and G/G and the T2 A/G and A/A genotypes (P=.0013 and P=.008, respectively) but not S1 and ST+4, increased the risk of asthma when using the best fit dominant model. Strong linkage disequilibrium between T1 (rs2280091) and T2 (rs2280090) was observed (r2=0.83; D'=0.95; P < .001). The haplotype G-A-A-C was significantly more frequent in asthmatics, thus supporting the association of T1 G-allele and T2 A-allele with increased predisposition to asthma (P=.007).
  
  
  CONCLUSIONS
  T1 A/G and T2 G/A ADAM33 polymorphisms, but not S1 or ST+4, were significantly associated with asthma development in Saudi children, like those reported for white and Hispanic populations in the United States.
authors.affiliation: Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Arwa Ishaq
authors.initials: AI
authors.lastname: Al-Khayyat
authors.forename: Mohammed
authors.initials: M
authors.lastname: Al-Anazi
authors.forename: Arjumand
authors.initials: A
authors.lastname: Warsy
authors.forename: Alejandro
authors.initials: A
authors.lastname: Vazquez-Tello
authors.forename: Abdullah Mohammed
authors.initials: AM
authors.lastname: Alamri
authors.forename: Rabih
authors.initials: R
authors.lastname: Halwani
authors.forename: Abdullah
authors.initials: A
authors.lastname: Alangari
authors.forename: Abdurrahman
authors.initials: A
authors.lastname: Al-Frayh
authors.forename: Qutayba
authors.initials: Q
authors.lastname: Hamid
authors.forename: Saleh
authors.initials: S
authors.lastname: Al-Muhsen
mesh_terms: D051722:ADAM Proteins / Q000235:genetics*; D001249:Asthma / Q000453:epidemiology* / Q000235:genetics*; D002648:Child; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012529:Saudi Arabia / Q000453:epidemiology
chemical_list: D051722:ADAM Proteins; C450441:ADAM33 protein, human