Genetic predisposition to the development of congenital heart diseases: Role of xenobiotic biotransformation genes

Abstract

Congenital heart diseases are one of the most common multi-factorial fetal abnormalities caused by a complex of endo-and exogenous factors. It is known that mutations in xenobiotic biotransformation genes can be associated with the pathogenesis of congenital heart diseases. In the presented research, 131 children with congenital heart diseases and 101 women having children with this pathology were included in the study group. In control group, 103 healthy children and their mothers were included. Single-nucleotide polymorphisms in the xenobiotic biotransformation genes CYP1A1 (rs1048943), CYP1A2 (rs762551), GSTP1 (rs6591256, rs1871042 and rs17593068) were detected by the real-time polymerase chain reaction. Gene-gene interactions were determined using the Multifactor Dimensionality Reduction method. We obtained no difference in the frequency of CYP1A1, CYP1A2 and GSTP1 between the study and control groups. At the same time, the genetic combinations GSTP1 (rs6591256)-GSTP1 (rs1871042) and GSTP1 (rs6591256)-GSTP1 (rs1871042)-CYP1A1 (rs1048943) in women; and GSTP1 (rs1793068)-GSTP1 (rs6591256)-GSTP1 (rs1871042)-CYP1A1 (rs1048943)-CYP1A2 (rs762551) in children contribute to the pathogenesis of congenital heart diseases.

Genome-wide Association Study of Caffeine Consumption Using Coriell Personalized Medicine Collaborative Data

“…Health outcomes that have been linked to coffee, caffeine consumption, and variants in CYP1A2 include hypertension, fasting glucose, and blood pressure [74][75][76]. Variants in CYP1A1 and CYP1A2, in combination with variants in other xenobiotic genes, have been associated with increased risk of congenital heart disease [77]. Another suggestive association implicates rs572614 on chromosome 18, which is located in an intron region 77K base pairs downstream of the LAMA1 gene (OMIM 150320) that encodes for the laminin A glycoprotein involved in structural scaffolding of many tissues including salivary Glands [78].…”