How Genetic and Environmental Factors Impact Risk of Orofacial Clefts in the Philippines
Hot Metal Campus researchers, including Mary L. Marazita, PhD, and Seth Weinberg, PhD, from UPitt’s Center for Craniofacial and Dental Genetics, as well as the Schools of Medicine and Public Health, are investigating the interaction between maternal smoking and vitamin use, and how these factors influence genes to cause orofacial clefts in Filipinos.
An orofacial cleft (OFC) is a congenital disability that results in an opening or split in the roof of the mouth and/or lip. OFCs impact one in 700 births worldwide, and the majority of these cases present as a cleft lip without a cleft palate (CL/P). The prevalence of OFCs in the Philippines is even higher, with one in 500 newborns affected by CL/P alone. Additionally, the rate of CL/P is lower for those with a high socioeconomic status in the Philippines, with only one in 1,000 newborns affected. Despite the high rates of CL/P in the Philippines and the presence of differences in risk between socioeconomic statuses, the genetic and environmental influences of CL/P risk in the Philippines have not been substantially researched before this study.
This gene-environment interaction study included 540 Filipino children with CL/P and 260 without the condition. They analyzed genetic data and detected gene-environment interaction from participants using three complementary methods:
A 1df G × E test, which determines the interaction between a singular gene and an environmental factor.
A unified 3df test, which examines three different possibilities of the interaction.
The two-step EDGE approach involves screening for and analyzing subtle interactions.
Although no genome-wide interactions were found, the study discovered 11 gene regions (or loci) that interacted with smoking and 24 that interacted with vitamin use. Of the 11 interactions with smoking, one was FEZF1, which influences nervous system development. TWIST2, a gene that is part of the early development of the face, was also influenced by maternal smoking. CECR2, which is essential for the development of the face and brain, as well as FURIN, a crucial factor in embryonic development, were found to interact with vitamin use.
The researchers have identified gene-environment interactions that have not been previously reported, regarding the influence of smoking and vitamin use on the development of C/P. These discoveries encourage further examination in the under-researched area of risks for OFCs in countries with a high prevalence, such as the Philippines. Additional research has the potential to help reduce risk and further understanding of how to narrow the gap in risk between different socioeconomic classes.
Read the full paper here.