MTHFR 677TT alone and IRF6 820GG together with MTHFR 677CT, but not MTHFR A1298C, are risks for nonsyndromic cleft lip with or without cleft palate in an Indian population.

To determine the association of three SNPs, IRF6 G820A, MTHFR C677T, and MTHFR A1298C, with nonsyndromic cleft lip with or without cleft palate (NSCL/P) in an Indian population. A total of 323 NSCL/P patients, 116 of their mothers, 108 of their fathers, and 214 normal controls have been examined for the above three SNPs. Frequency of IRF6 GG was 65% in controls, 78% in cases, 84% in case-fathers, and 80% in case-mothers. MTHFR 677T homozygosity was lower than 1% in controls and unaffected parents, while in the group of probands it was much higher (3.4%; OR 4.30). The frequency of CT genotype was also high in the cases and case-mothers (OR 1.89 and 2.2, respectively). MTHFR A1298C did not reveal a statistically significant deviation in allele and genotype frequencies. While MTHFR 677T homozygotes show a significant association with NSCL/P, heterozygotes 677CT are minor risk factors. MTHFR A1298C does not show a risk in any combination of alleles. IRF6 820GG too forms a minor risk. However, combined genotypes IRF6 GG/MTHFR 677CT together form greater risk for NSCL/P.