title: Evidence of gene-environment interaction for the RUNX2 gene and environmental tobacco smoke in controlling the risk of cleft lip with/without cleft palate.
abstract: This study examined the association between 49 markers in the Runt-related transcription factor 2 (RUNX2) gene and nonsyndromic cleft lip with/without cleft palate (CL/P) among 326 Chinese case-parent trios, while considering gene-environment (GxE) interaction and parent-of-origin effects. Five single-nucleotide polymorphisms (SNPs) showed significant evidence of linkage and association with CL/P and these results were replicated in an independent European sample of 825 case-parent trios. We also report compelling evidence for interaction between markers in RUNX2 and environmental tobacco smoke (ETS). Although most marginal SNP effects (i.e., ignoring maternal exposures) were not statistically significant, eight SNPs were significant when considering possible interaction with ETS when testing for gene (G) and GxE interaction simultaneously or when considering GxE alone. Independent samples from European populations showed consistent evidence of significant GxETS interaction at two SNPs (rs6904353 and rs7748231). Our results suggest genetic variation in RUNX2 may influence susceptibility to CL/P through interacting with ETS.
authors.affiliation: Peking University School of Public Health, Beijing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wu
authors.forename: M Daniele
authors.initials: MD
authors.lastname: Fallin
authors.forename: Min
authors.initials: M
authors.lastname: Shi
authors.forename: Ingo
authors.initials: I
authors.lastname: Ruczinski
authors.forename: Kung Yee
authors.initials: KY
authors.lastname: Liang
authors.forename: Jacqueline B
authors.initials: JB
authors.lastname: Hetmanski
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Roxann G
authors.initials: RG
authors.lastname: Ingersoll
authors.forename: Shangzhi
authors.initials: S
authors.lastname: Huang
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Ye
authors.forename: Yah-Huei
authors.initials: YH
authors.lastname: Wu-Chou
authors.forename: Philip K
authors.initials: PK
authors.lastname: Chen
authors.forename: Ethylin Wang
authors.initials: EW
authors.lastname: Jabs
authors.forename: Bing
authors.initials: B
authors.lastname: Shi
authors.forename: Richard
authors.initials: R
authors.lastname: Redett
authors.forename: Alan F
authors.initials: AF
authors.lastname: Scott
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Murray
authors.forename: Mary L
authors.initials: ML
authors.lastname: Marazita
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Munger
authors.forename: Terri H
authors.initials: TH
authors.lastname: Beaty
mesh_terms: D044466:Asian People / Q000235:genetics; D002681:China; D002971:Cleft Lip / Q000208:ethnology / Q000235:genetics*; D002972:Cleft Palate / Q000208:ethnology / Q000235:genetics*; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics*; D005060:Europe; D005260:Female; D059647:Gene-Environment Interaction; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D018811:Maternal Exposure; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D044465:White People / Q000235:genetics
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; C493709:RUNX2 protein, human; D014028:Tobacco Smoke Pollution