A case-control study of nonsyndromic oral clefts in Maryland

T. H. Beaty, H. Wang, J. B. Hetmanski, Y. T. Fan, J. S. Zeiger, K. Y. Liang, Y. F. Chiu, C. A. Vanderkolk, K. C. Seifert, E. A. Wulfsberg, G. Raymond, S. R. Panny, I. McIntosh

Research output: Contribution to journalArticle

Abstract

PURPOSE: 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 α (TGFα), transforming growth factor β3 (TGFβ3), 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. CONCLUSION: 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.

Original languageEnglish (US)
Pages (from-to)434-442
Number of pages9
JournalAnnals of epidemiology
Volume11
Issue number6
DOIs
StatePublished - Jul 26 2001

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Keywords

  • Familial Aggregation
  • MSX1
  • Maternal Alcohol Use
  • Maternal Smoking
  • Oral Clefts
  • Transforming Growth Factor α

ASJC Scopus subject areas

  • Epidemiology

Cite this

Beaty, T. H., Wang, H., Hetmanski, J. B., Fan, Y. T., Zeiger, J. S., Liang, K. Y., Chiu, Y. F., Vanderkolk, C. A., Seifert, K. C., Wulfsberg, E. A., Raymond, G., Panny, S. R., & McIntosh, I. (2001). A case-control study of nonsyndromic oral clefts in Maryland. Annals of epidemiology, 11(6), 434-442. https://doi.org/10.1016/S1047-2797(01)00222-8