Association of long interspersed nucleotide element-1 and interferon regulatory factor 6 methylation changes with nonsyndromic cleft lip with or without cleft palate.

OBJECTIVE: To examine the possible associations between methylation changes in the promoter regions of long interspersed nucleotide element-1 (LINE-1) and interferon regulatory factor 6 gene (IRF6) and nonsyndromic cleft lip with or without cleft palate (NSCL/P).

METHODS: A case-control investigation was performed to compare 37 infants affected by NSCL/Ps with 60 babies without cleft malformations. Their genomic DNA samples were obtained, and the LINE-1 and IRF6 methylation levels were measured by using Sequenom MassArray. Unconditional logistic regression was adopted to estimate the odds ratio.

RESULTS: Infants with NSCL/Ps had a higher methylation level at LINE-1 and IRF6 promoter regions than controls. High levels of LINE-1 (≥64.07%) and IRF6 (≥6.46%) methylation were associated with an increased risk of NSCL/P (LINE-1, OR = 2.63, 95% CI: 1.07-6.57; IRF6, OR = 4.73, 95% CI: 2.10-13.07), and the associations remained to be significant after adjusting for potential confounders. Similar associations were also found for cleft lip only, cleft lip, and palate.

CONCLUSION: Our study suggested that aberrant methylation of LINE-1 and IRF6 might contribute to the development of NSCL/Ps. Further studies are needed to replicate the findings.