The search for risk factors that contribute to the etiology of non-syndromic cleft lip with or without cleft palate (CL/P) in the Polish population

Abstract

Abstract Non-syndromic cleft lip with or without cleft palate (CL/P) has severe long-lasting adverse effects on both physical and psychological development. Although recent years have brought significant improvement in clinical treatment, our understanding of the etiology of this congenital anomaly is lagging. Many genes, genetic pathways, harmful exposures, as well as nutrient deficiencies have been implicated in abnormal palatogenesis. Extrapolating data regarding risk factors for CL/P from different populations is not always straightforward. This review gives an overview of knowledge about both environmental and genetic risk factors in the etiology of CL/P in the Polish population, which was originally presented in research papers by the author and collaborating investigators. The findings suggest a possible association between maternal consumption of α-tocopherol, retinol, zinc, citrulline, and dietary compounds contributing to methyl-group homeostasis and CL/P risk. Polymorphisms in BHMT1 and BHMT2 were significantly associated with decreased CL/P risk in the Polish population. Other interesting findings include associations of CL/P risk with polymorphisms in MTR, PCYT1A, ASS1, SLC 25A13, GSTM1, GSTT1, SUMO1 genes, and 8q24.21 loci. Reviewed research papers indicate interesting pathways and new candidate genes for further investigation, and partly confirm earlier findings according risk factors for orofacial clefts.