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Interferon Regulatory Factor 6 (IRF6) and Gene – Environment Interactions in Non-Syndromic Orofacial Cleft Cases in Saudi Arabia-A Case Control Study

Najlaa M Alamoudi*, Heba J Sabbagh, Nicola P Innes, Sherif Edris Ahmed, Azeez Butali, Eman Abdulbaset Alnamnakani, Sari Rabah, Mustafa A Hamdan, Nasir H Alhamlan, Fatma D Abdulhameed, Najat M Farsi, Ali H Hassan and Peter A Mossey

The association between interferon regulatory factor 6 (IRF6) and nonsyndromic orofacial cleft (NSOFC) is affected by ethnicity. Also, gene-environment interactions (GEI) may play an important role in its etiology.
Objectives: This case-control study investigated whether IRF6 gene variants were associated with NSOFC in Saudi Arabian population and whether the gene was affected by maternal environmental exposures.
Methods: We extracted DNA from saliva samples obtained from 171 infant–parent triad cases and 189 matched controls (age, gender, and location) from January 2010–December 2011; this study included a total of 11 referral hospitals in Saudi Arabia. IRF6 (rs2013162, rs2235375, and rs2235371) polymorphisms were genotyped using restriction-digestion polymerase chain reaction. Data on environmental exposures, for GEI analyses, were collected through questionnaire-led interviews with parents.
Results: We found statistically significant over transmission of the common IRF6 rs2013162 allele among cleft lip with or without palate CL(P) cases. No associations were found for either of the other two IRF6 SNPs. Maternal exposure to antipyretics, folic acid, fever, antibiotics, illnesses, common cold/flu, paternal water pipe smoking, stress, x-rays, and/or chemicals could significantly interact with the maternal IRF6 (rs2013162 and rs2235375) gene variants, affecting the likelihood of having an offspring with NSOFC.
Conclusion: The common allele at IRF6 rs2013162 was significantly over transmitted among CL(P) cases. This study provides hypotheses for future investigations into genetic and environmental factors and their interaction in the etiology of NSOFC.