Association between C677T and A1298C MTHFR gene polymorphism and nonsyndromic orofacial clefts in the Turkish population: a case-parent study

Turk J Pediatr. 2012 Nov-Dec;54(6):617-25.

Abstract

Two common MTHFR gene polymorphisms (C677T and A1298C) have been implicated in the etiology of nonsyndromic cleft lip/palate (nsCL/P). To investigate the genotype association among nsCL/P in the Turkish population, 56 case-parent trios were recruited into the study. Genotype frequencies were compared to two groups of controls from the same population. A total of 46 case-parent trios were included in transmission disequilibrium test (TDT) analysis. The mothers of the study group had a higher frequency of 677TT genotype, with a three-fold increased risk of having nsCL/P offspring (odds ratio [OR]: 3.14, p=0.03). The combined 677CT/1298AC genotype was also common among these mothers (28%), but it did not reach statistical significance (OR: 2.27, p=0.07). TDT analysis for (C677T) T allele transmission did not reveal a significant association. In conclusion, mothers carrying 677TT genotype or with 677CT/1298AC combined genotype have increased risk of having nsCL/P offspring; therefore, higher periconceptional folic acid supplementation should be advised for decreasing the recurrence risk.

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Brain / abnormalities*
  • Brain / metabolism
  • Child
  • Child, Preschool
  • Cleft Lip / epidemiology
  • Cleft Lip / genetics*
  • Cleft Lip / metabolism
  • Cleft Palate / epidemiology
  • Cleft Palate / genetics*
  • Cleft Palate / metabolism
  • DNA / genetics*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Incidence
  • Infant
  • Infant, Newborn
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Methylenetetrahydrofolate Reductase (NADPH2) / metabolism
  • Parents*
  • Polymorphism, Genetic*
  • Risk Factors
  • Turkey / epidemiology
  • Young Adult

Substances

  • DNA
  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)

Supplementary concepts

  • Orofacial Cleft 1