Abstract Title

Association of IRF6 rs642961 variant with Cleft Phenotype in Nonsyndromic Cleft Lip and Palate

Lead Author Affiliation

Craniofacial Genetics

Lead Author Status

DDS Year 2

Expected Graduation Date

2020

Presentation Category

Research

Introduction/Context/Diagnosis

Several susceptibility genes (AKA candidate genes) MTHFR, TGFA, IRF6, MSX1, TGFB3 and others have been found associated with nonsyndromic cleft lip with or without cleft palate (NCL/P), one of the most common birth defects around the world. Among these genes, Interferon Regulatory Factor 6 (IRF6), a member of the IRF family of transcription factors, plays an important role in orofacial development and its variants have been found associated with NCL/P. Several studies have established IRF6 mutations as a monogenic cause of syndromic cleft lip and palate, namely Van der Woude syndrome. In NCL/P, IRF6 may be a part of a complex multifactorial etiology. Our objective was to conduct a pilot study to determine, if an IRF6 gene variant was associated with NCL/P in Karaikal, India.

Methods/Treatment Plan

A case-control design (cases = 235; controls = 164) was chosen for this study. The group of cases comprised 75 cases of cleft lip (CL), 141 cases of cleft lip and palate (CLP), and 19 cases on cleft palate (CP). The control group consisted of 164 individuals with no cleft from the same location. DNA was isolated from dry blood blots on filter paper. Genotypes of IRF6 rs642961 variant were determined using rtPCR. Genotype proportions and allele frequencies were compared between cases and controls and between CL and CLP.

Results/Outcome

Proportions of genotypes in cases and controls were not significantly different. Cases GG=62.1%, GA=31.8, AA=5.1%; and controls GG=61.6%, GA=31.7%, AA=6.7%. There was also no significant difference found between CL and CLP cases in proportions of genotypes. Mutated allele A was observed in a higher frequency in controls (0.226), compared to cases (0.184), but this difference was not statistically significant. However, when we compared allele frequencies between CL and CLP cases, the mutated allele A was observed in a higher frequency in CL – 0.273 than in CLP – 0.188. This difference was statistically significant (p=0.04).

Significance/Conclusions

There has been no study exploring associations of IRF6 variants with NCL/P in India. Results of this study suggest that different cleft phenotypes may be associated with a specific gene variant and thus related to a variable genetic susceptibility for orofacial clefts. Our study will continue analyzing IRF6 rs642961variant and other IRF6 variants in Indian population.

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Association of IRF6 rs642961 variant with Cleft Phenotype in Nonsyndromic Cleft Lip and Palate

Several susceptibility genes (AKA candidate genes) MTHFR, TGFA, IRF6, MSX1, TGFB3 and others have been found associated with nonsyndromic cleft lip with or without cleft palate (NCL/P), one of the most common birth defects around the world. Among these genes, Interferon Regulatory Factor 6 (IRF6), a member of the IRF family of transcription factors, plays an important role in orofacial development and its variants have been found associated with NCL/P. Several studies have established IRF6 mutations as a monogenic cause of syndromic cleft lip and palate, namely Van der Woude syndrome. In NCL/P, IRF6 may be a part of a complex multifactorial etiology. Our objective was to conduct a pilot study to determine, if an IRF6 gene variant was associated with NCL/P in Karaikal, India.