MTHFR c.677C>T is a risk factor for non-syndromic cleft lip with or without cleft palate in Chile

Oral Dis. 2016 Oct;22(7):703-8. doi: 10.1111/odi.12533. Epub 2016 Aug 1.


Objective: The functional variant within the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene c.677C>T, producing alterations in folate metabolism, has been associated with the risk of non-syndromic cleft lip with or without cleft palate (NSCL/P). We assessed this association in a Chilean population using a combined analysis of case-control and case-parent trio samples.

Subjects and methods: Samples of 165 cases and 291 controls and 121 case-parent trios (sharing the cases) were genotyped. Odds ratio (OR) was estimated for case-control (allele and genotype frequency differences), and this result was confirmed by allele transmission distortion in trios. Due to that these samples are not independent, a combined OR was also computed. Maternal genotype effect was additionally evaluated based on a log-linear method.

Results: Borderline but not significant OR (1.28; CI 0.97-1.69) was observed for risk allele (T) in the case-control sample. However, triad sample showed a significant association (OR 1.56: CI 1.09-2.25) which was confirmed by the combined OR (1.37; CI 1.11-1.71). Maternal genotype has been also associated with the phenotype (P = 0.002).

Conclusions: In contrast to previous reports considering Chilean subjects, our results demonstrated that the offspring and maternal genotypes for MTHFR c.677C>T variant are strongly associated with NSCL/P in this Chilean population.

Keywords: MTHFR; Non-syndromic cleft lip with or without cleft palate; case-control; case-parent trios.

MeSH terms

  • Adolescent
  • Adult
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Chile
  • Cleft Palate / genetics*
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Odds Ratio
  • Risk Factors


  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)