title: A case-control study of nonsyndromic oral clefts in Maryland.
abstract: OBJECTIVE
  Isolated, nonsyndromic oral clefts cases (n = 171) and unaffected controls (n = 182) were used to identify both genetic and environmental risk factors.
  
  
  METHODS
  Infants born in Maryland between 1992 to 1998 with an isolated, nonsyndromic oral cleft [cleft lip (CL), cleft lip and palate (CLP), or cleft palate (CP)] were recruited and exposure plus family history data were collected. Controls were unaffected infants. DNA was collected from all cases and their parents, plus controls.
  
  
  RESULTS
  No statistically significant association was found between any of the following: maternal smoking, vitamin use, urinary tract infection, or recreational drug use in either univariate analysis or after adjusting for maternal age and education. More control mothers reported alcohol use during the critical time period of pregnancy (one month before conception through the first trimester) as compared to case mothers. There was a 10-fold increase in risk to siblings of cases as compared to siblings of controls. Markers at four candidate genes were examined: transforming growth factor alpha (TGF alpha), transforming growth factor beta 3 (TGF beta 3), MSX1, and BCL3. Only MSX1 showed significant differences in allele frequencies between CP cases and controls. MSX1 also showed significant evidence of linkage disequilibrium with a susceptibility gene controlling risk for CP.
  
  
  CONCLUSIONS
  Most environmental risk factors examined here gave little evidence of association with risk to isolated, nonsyndromic oral clefts, although any alcohol consumption seemed protective. MSX1 showed evidence of linkage disequilibrium in both case-control and case-parent trio analysis.
authors.affiliation: The Johns Hopkins University, Baltimore, MD, USA.
authors.forename: T H
authors.initials: TH
authors.lastname: Beaty
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.forename: J B
authors.initials: JB
authors.lastname: Hetmanski
authors.forename: Y T
authors.initials: YT
authors.lastname: Fan
authors.forename: J S
authors.initials: JS
authors.lastname: Zeiger
authors.forename: K Y
authors.initials: KY
authors.lastname: Liang
authors.forename: Y F
authors.initials: YF
authors.lastname: Chiu
authors.forename: C A
authors.initials: CA
authors.lastname: Vanderkolk
authors.forename: K C
authors.initials: KC
authors.lastname: Seifert
authors.forename: E A
authors.initials: EA
authors.lastname: Wulfsberg
authors.forename: G
authors.initials: G
authors.lastname: Raymond
authors.forename: S R
authors.initials: SR
authors.lastname: Panny
authors.forename: I
authors.initials: I
authors.lastname: McIntosh
mesh_terms: D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002971:Cleft Lip / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics; D002972:Cleft Palate / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D016015:Logistic Models; D008396:Maryland / Q000453:epidemiology; D009010:Monte Carlo Method; D012307:Risk Factors