Folate and clefts of the lip and palate - A UK-based case-control study: Part II: Biochemical and genetic analysis

J. Little, M. Gilmour, P. A. Mossey, D. FitzPatrick, A. Cardy, J. Clayton-Smith, A. Hill, S. J. Duthie, A. E. Fryer, A. M. Molloy, J. M. Scott, ITS MAGIC Collaboration

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Objective: To investigate associations between nonsyndromic oral clefts and biochemical measures of folate status and the MTHFR C677T variant in the United Kingdom, where there has been no folic acid fortification program.

Method: Dietary details were obtained from the mothers of 112 cases of cleft lip with or without cleft palate (CL +/- P), 78 cleft palate only (CP) cases, and 248 unaffected infants. Infant and parental MTHFR C677T genotype was determined. Red blood cell (RBC) and serum folate and homocysteine levels were assessed in 12-month postpartum blood samples from a subset of mothers. The data were analyzed by logistic and log-linear regression methods.

Results: There was an inverse association between CL +/- P and maternal MTHFR CT (odds ratio [OR] = 0.5, 95% confidence interval [CI] = 0.31-0.95) and TT (OR = 0.6, 95% CI = 0.21-1.50) genotypes, with similar risk estimates for CP. There was no clear association with infant MTHFR genotype. Higher levels of maternal postpartum RBC and serum folate were associated with a lower risk for CL +/- P and an increased risk for CP. Higher levels of serum homocysteine were associated with a slightly increased risk for both CL +/- P and CP.

Conclusion: While the inverse relation between the mother's having the MTHFR C677T variant and both CL +/- P and CP suggests perturbation of maternal folate metabolism is of etiological importance, contrasting relations between maternal postpartum levels of RBC and serum folate by type of cleft are difficult to explain.

Original languageEnglish
Pages (from-to)428-438
Number of pages11
JournalCleft Palate-Craniofacial Journal
Volume45
Issue number4
DOIs
Publication statusPublished - Jul 2008

Keywords

  • case control
  • folic acid
  • MTHFR
  • cleft lip
  • cleft palate
  • polymorphism
  • red cell folate
  • serum folate
  • homocysteine
  • case-parent triads
  • methylenetetrahydrofolate reductase polymorphisms
  • infant C677T mutation
  • orofacial clefts
  • risk-factor
  • oral clefts
  • MTHFR gene
  • plasma homocysteine
  • colorectal-cancer
  • candidate genes

Cite this

Little, J., Gilmour, M., Mossey, P. A., FitzPatrick, D., Cardy, A., Clayton-Smith, J., ... ITS MAGIC Collaboration (2008). Folate and clefts of the lip and palate - A UK-based case-control study: Part II: Biochemical and genetic analysis. Cleft Palate-Craniofacial Journal, 45(4), 428-438. https://doi.org/10.1597/06-151.1

Folate and clefts of the lip and palate - A UK-based case-control study: Part II: Biochemical and genetic analysis. / Little, J.; Gilmour, M.; Mossey, P. A.; FitzPatrick, D.; Cardy, A.; Clayton-Smith, J.; Hill, A.; Duthie, S. J.; Fryer, A. E.; Molloy, A. M.; Scott, J. M.; ITS MAGIC Collaboration.

In: Cleft Palate-Craniofacial Journal, Vol. 45, No. 4, 07.2008, p. 428-438.

Research output: Contribution to journalArticle

Little, J, Gilmour, M, Mossey, PA, FitzPatrick, D, Cardy, A, Clayton-Smith, J, Hill, A, Duthie, SJ, Fryer, AE, Molloy, AM, Scott, JM & ITS MAGIC Collaboration 2008, 'Folate and clefts of the lip and palate - A UK-based case-control study: Part II: Biochemical and genetic analysis' Cleft Palate-Craniofacial Journal, vol. 45, no. 4, pp. 428-438. https://doi.org/10.1597/06-151.1
Little, J. ; Gilmour, M. ; Mossey, P. A. ; FitzPatrick, D. ; Cardy, A. ; Clayton-Smith, J. ; Hill, A. ; Duthie, S. J. ; Fryer, A. E. ; Molloy, A. M. ; Scott, J. M. ; ITS MAGIC Collaboration. / Folate and clefts of the lip and palate - A UK-based case-control study: Part II: Biochemical and genetic analysis. In: Cleft Palate-Craniofacial Journal. 2008 ; Vol. 45, No. 4. pp. 428-438.
@article{8a7ae34badbd44908c391067a54f36ee,
title = "Folate and clefts of the lip and palate - A UK-based case-control study: Part II: Biochemical and genetic analysis",
abstract = "Objective: To investigate associations between nonsyndromic oral clefts and biochemical measures of folate status and the MTHFR C677T variant in the United Kingdom, where there has been no folic acid fortification program.Method: Dietary details were obtained from the mothers of 112 cases of cleft lip with or without cleft palate (CL +/- P), 78 cleft palate only (CP) cases, and 248 unaffected infants. Infant and parental MTHFR C677T genotype was determined. Red blood cell (RBC) and serum folate and homocysteine levels were assessed in 12-month postpartum blood samples from a subset of mothers. The data were analyzed by logistic and log-linear regression methods.Results: There was an inverse association between CL +/- P and maternal MTHFR CT (odds ratio [OR] = 0.5, 95{\%} confidence interval [CI] = 0.31-0.95) and TT (OR = 0.6, 95{\%} CI = 0.21-1.50) genotypes, with similar risk estimates for CP. There was no clear association with infant MTHFR genotype. Higher levels of maternal postpartum RBC and serum folate were associated with a lower risk for CL +/- P and an increased risk for CP. Higher levels of serum homocysteine were associated with a slightly increased risk for both CL +/- P and CP.Conclusion: While the inverse relation between the mother's having the MTHFR C677T variant and both CL +/- P and CP suggests perturbation of maternal folate metabolism is of etiological importance, contrasting relations between maternal postpartum levels of RBC and serum folate by type of cleft are difficult to explain.",
keywords = "case control, folic acid, MTHFR, cleft lip, cleft palate, polymorphism, red cell folate, serum folate, homocysteine, case-parent triads, methylenetetrahydrofolate reductase polymorphisms, infant C677T mutation, orofacial clefts, risk-factor, oral clefts, MTHFR gene, plasma homocysteine, colorectal-cancer, candidate genes",
author = "J. Little and M. Gilmour and Mossey, {P. A.} and D. FitzPatrick and A. Cardy and J. Clayton-Smith and A. Hill and Duthie, {S. J.} and Fryer, {A. E.} and Molloy, {A. M.} and Scott, {J. M.} and {ITS MAGIC Collaboration}",
year = "2008",
month = "7",
doi = "10.1597/06-151.1",
language = "English",
volume = "45",
pages = "428--438",
journal = "Cleft Palate-Craniofacial Journal",
issn = "1055-6656",
publisher = "American Cleft Palate Craniofacial Association",
number = "4",

}

TY - JOUR

T1 - Folate and clefts of the lip and palate - A UK-based case-control study: Part II: Biochemical and genetic analysis

AU - Little, J.

AU - Gilmour, M.

AU - Mossey, P. A.

AU - FitzPatrick, D.

AU - Cardy, A.

AU - Clayton-Smith, J.

AU - Hill, A.

AU - Duthie, S. J.

AU - Fryer, A. E.

AU - Molloy, A. M.

AU - Scott, J. M.

AU - ITS MAGIC Collaboration

PY - 2008/7

Y1 - 2008/7

N2 - Objective: To investigate associations between nonsyndromic oral clefts and biochemical measures of folate status and the MTHFR C677T variant in the United Kingdom, where there has been no folic acid fortification program.Method: Dietary details were obtained from the mothers of 112 cases of cleft lip with or without cleft palate (CL +/- P), 78 cleft palate only (CP) cases, and 248 unaffected infants. Infant and parental MTHFR C677T genotype was determined. Red blood cell (RBC) and serum folate and homocysteine levels were assessed in 12-month postpartum blood samples from a subset of mothers. The data were analyzed by logistic and log-linear regression methods.Results: There was an inverse association between CL +/- P and maternal MTHFR CT (odds ratio [OR] = 0.5, 95% confidence interval [CI] = 0.31-0.95) and TT (OR = 0.6, 95% CI = 0.21-1.50) genotypes, with similar risk estimates for CP. There was no clear association with infant MTHFR genotype. Higher levels of maternal postpartum RBC and serum folate were associated with a lower risk for CL +/- P and an increased risk for CP. Higher levels of serum homocysteine were associated with a slightly increased risk for both CL +/- P and CP.Conclusion: While the inverse relation between the mother's having the MTHFR C677T variant and both CL +/- P and CP suggests perturbation of maternal folate metabolism is of etiological importance, contrasting relations between maternal postpartum levels of RBC and serum folate by type of cleft are difficult to explain.

AB - Objective: To investigate associations between nonsyndromic oral clefts and biochemical measures of folate status and the MTHFR C677T variant in the United Kingdom, where there has been no folic acid fortification program.Method: Dietary details were obtained from the mothers of 112 cases of cleft lip with or without cleft palate (CL +/- P), 78 cleft palate only (CP) cases, and 248 unaffected infants. Infant and parental MTHFR C677T genotype was determined. Red blood cell (RBC) and serum folate and homocysteine levels were assessed in 12-month postpartum blood samples from a subset of mothers. The data were analyzed by logistic and log-linear regression methods.Results: There was an inverse association between CL +/- P and maternal MTHFR CT (odds ratio [OR] = 0.5, 95% confidence interval [CI] = 0.31-0.95) and TT (OR = 0.6, 95% CI = 0.21-1.50) genotypes, with similar risk estimates for CP. There was no clear association with infant MTHFR genotype. Higher levels of maternal postpartum RBC and serum folate were associated with a lower risk for CL +/- P and an increased risk for CP. Higher levels of serum homocysteine were associated with a slightly increased risk for both CL +/- P and CP.Conclusion: While the inverse relation between the mother's having the MTHFR C677T variant and both CL +/- P and CP suggests perturbation of maternal folate metabolism is of etiological importance, contrasting relations between maternal postpartum levels of RBC and serum folate by type of cleft are difficult to explain.

KW - case control

KW - folic acid

KW - MTHFR

KW - cleft lip

KW - cleft palate

KW - polymorphism

KW - red cell folate

KW - serum folate

KW - homocysteine

KW - case-parent triads

KW - methylenetetrahydrofolate reductase polymorphisms

KW - infant C677T mutation

KW - orofacial clefts

KW - risk-factor

KW - oral clefts

KW - MTHFR gene

KW - plasma homocysteine

KW - colorectal-cancer

KW - candidate genes

U2 - 10.1597/06-151.1

DO - 10.1597/06-151.1

M3 - Article

VL - 45

SP - 428

EP - 438

JO - Cleft Palate-Craniofacial Journal

JF - Cleft Palate-Craniofacial Journal

SN - 1055-6656

IS - 4

ER -