Folate-related gene polymorphisms as risk factors for cleft lip and cleft palate.
Item Type:Journal Article
Citation:J.L. Mills, A.M. Molloy, A. Parle-McDermott, J.F. Troendle, L.C. Brody, M.R. Conley, C. Cox, F. Pangilinan, D.J. Orr, M. Earley, E. McKiernan, E.C. Lynn, A. Doyle, J.M. Scott, P.N. Kirke `Folate-related gene polymorphisms as risk factors for cleft lip and cleft palate? Birth Defects Research Part A Clinical and Molecular Teratology, 82, (9), 2008, pp 636 - 643
Folate-related gene polymorphisms as risk factors for cleft lip and cleft palate.pdf (published (publisher copy) peer-reviewed) 345.0Kb
BACKGROUND?Cleft lip with or without cleft palate (CLP) and cleft palate only (CPO) have an inherited component and, many studies suggest, a relationship with folate. Attempts to find folaterelated genes associated with clefts have, however, often been inconclusive. This study examined four SNPs related to folate metabolism (MTHFR 677 C?T, MTHFR 1298 A?C, MTHFD1 1958 G?A, and TC II 776 C?G) in a large Irish population to clarify their relationship with clefts. METHODS?Cases and their parents were recruited from major surgical centers performing cleft repairs in Ireland and a support organization. Data on risk factors, medical history, and DNA were collected. Controls were pregnant women from the greater Dublin area (n = 1,599). RESULTS?CLP cases numbered 536 and CPO cases 426 after exclusions. CPO mothers were significantly more likely than controls to be MTHFR 677 TT, OR 1.50 (95% CI: 1.05?2.16; p = .03). Log-linear analysis showed a borderline association (p = .07). Isolated CPO case mothers were significantly more likely than controls to be homozygous for the MTHFD1 1958 G?A variant, OR 1.50 (95%CI: 1.08?2.09; p = .02). When multiple cases were added, both CPO cases and case mothers were significantly more likely to be AA (p = .02 and p = .007, respectively). The CLP case-control and mother-control analyses also showed significant effects, ORs 1.38 (95% CI: 1.05?1.82; p = .03) and 1.39 (95% CI: 1.04?1.85; p = .03), respectively. CONCLUSIONS?Associations were found for both CPO and CLP and MTHFD1 1958 G?A in cases and case mothers. MTHFR 677 C?T could be a maternal risk factor for clefts but the association was not strong. Because multiple comparisons were made, these findings require additional investigation. Given the known association between MTHFD1 1958 G?A and NTDs, these findings should be explored in more detail.
Health Research Board
Author: MOLLOY, ANNE MARIE
Type of material:Journal Article
Series/Report no:Birth Defects Research Part A Clinical and Molecular Teratology.
Availability:Full text available
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MOLLOY, ANNE; SCOTT, JOHN; ORR, DAVID (2008)BACKGROUND Cleft lip with or without cleft palate (CLP) and cleft palate only (CPO) have an inherited component and, many studies suggest, a relationship with folate. Attempts to find folate-related genes associated ...
A genome-wide association study of cleft lip with and without cleft palate identifies risk variants near MAFB and ABCA4. MOLLOY, ANNE; SCOTT, JOHN (2010)Case-parent trios were used in a genome-wide association study of cleft lip with and without cleft palate. SNPs near two genes not previously associated with cleft lip with and without cleft palate (MAFB, most significant ...
Testing reported associations of genetic risk factors for oral clefts in a large Irish study population. MOLLOY, ANNE; SCOTT, JOHN; ORR, DAVID (2010)BACKGROUND Suggestive, but not conclusive, studies implicate many genetic variants in oral cleft etiology. We used a large, ethnically homogenous study population to test whether reported associations between nonsyndromic ...