title: Local genotype influences DNA methylation at two asthma-associated regions, 5q31 and 17q21, in a founder effect population.
abstract: BACKGROUND
  Two asthma-associated regions 17q12-q21 and 5q31.1 harbour genes that show strong effect of genotype on expression levels. DNA methylation has an important role in gene regulation; therefore, we examined DNA methylation at promoters of 12 genes from 5q31 and 17q12-q21 regions. Our goal was to determine whether DNA methylation was associated with predisposition to asthma and whether such a relationship was independent from genetic association.
  
  
  METHODS
  Using sodium bisulfite sequencing and pyrosequencing methylation assays, we examined the effect of genotype on DNA methylation in peripheral blood cells from individuals from the Saguenay-Lac-Saint-Jean asthma familial collection and lymphoblastoid cell lines.
  
  
  RESULTS
  The local genotype influenced methylation levels of solute carrier family 22 (organic 3 cation/carnitine transporter) member 5 (SLC22A5), zona pellucida binding protein 2 (ZPBP2) and gasdermin A (GSDMA) promoter regions. The genotype had a dominant effect on ZPBP2 and GSDMA methylation with lower methylation levels in individuals that carry the asthma-predisposing alleles. Males also had lower methylation at the ZPBP2 promoter than females. We did not observe an effect of asthma status that would be independent of the genotype and the sex effects in the GSDMA, ZPBP2 and SLC22A5 regions; however, GSDMA and ZPBP2 data were suggestive of interaction between asthma and methylation levels in females and SLC22A5 in males.
  
  
  CONCLUSIONS
  The local genotype influences methylation levels at SLC22A5 and ZPBP2 promoters independently of the asthma status. Further studies are necessary to confirm the relationship between GSDMA-ZPBP2 and SLC22A5 methylation and asthma in females and males separately.
authors.affiliation: Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
authors.forename: Abeer
authors.initials: A
authors.lastname: Al Tuwaijri
authors.affiliation: Département des sciences fondamentales, Université du Québec à Chicoutimi, Chicoutimi, Quebec, Canada.
authors.forename: Valérie
authors.initials: V
authors.lastname: Gagné-Ouellet
authors.affiliation: Département des sciences fondamentales, Université du Québec à Chicoutimi, Chicoutimi, Quebec, Canada.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Madore
authors.affiliation: Département des sciences fondamentales, Université du Québec à Chicoutimi, Chicoutimi, Quebec, Canada.
authors.forename: Catherine
authors.initials: C
authors.lastname: Laprise
authors.affiliation: Department of Human Genetics, McGill University, Montreal, Quebec, Canada Department of Obstetrics and Gynecology, McGill University, Montreal, Quebec, Canada The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Naumova
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002886:Chromosomes, Human, Pair 17; D002895:Chromosomes, Human, Pair 5; D019175:DNA Methylation / Q000235:genetics*; D004527:Egg Proteins / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D027701:Organic Cation Transport Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D000074058:Solute Carrier Family 22 Member 5; D000094524:Gasdermins
chemical_list: D004527:Egg Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D027701:Organic Cation Transport Proteins; D000074058:Solute Carrier Family 22 Member 5; C485887:GSDMA protein, human; D000094524:Gasdermins; C492020:SLC22A5 protein, human; C479482:ZPBP2 protein, human
keywords: Asthma; Complex traits; Epigenetics; Genetics