Multifactor dimensionality reduction analysis to elucidate the cross-talk between one-carbon and xenobiotic metabolic pathways in multi-disease models

Abstract

Putatively functional polymorphisms of one-carbon and xenobiotic metabolic pathways influence susceptibility for wide spectrum of diseases. The current study was aimed to explore gene-gene interactions among these two metabolic pathways in four diseases i.e. breast cancer, systemic lupus erythematosus (SLE), coronary artery disease (CAD) and Parkinson's disease (PD). Multifactor dimensionality reduction analysis was carried out on four case-control datasets. Cross-talk was observed between one-carbon and xenobiotic pathways in breast cancer (RFC 80 G>A, COMT H108L and TYMS 5'-UTR 28 bp tandem repeat) and SLE (CYP1A1 m1, MTRR 66 A>G and GSTT1). Gene-gene interactions within one-carbon metabolic pathway were observed in CAD (GCPII 1561 C>T, SHMT 1420 C>T and MTHFR 677 C>T) and PD (cSHMT 1420 C>T, MTRR 66 A>G and RFC1 80 G>A). These interaction models showed good predictability of risk for PD (The area under the receiver operating characteristic curve (C) = 0.83) and SLE (C = 0.73); and moderate predictability of risk for breast cancer (C = 0.64) and CAD (C = 0.63). Cross-talk between one-carbon and xenobiotic pathways was observed in diseases with female preponderance. Gene-gene interactions within one-carbon metabolic pathway were observed in diseases with male preponderance.

Systems Pharmacogenomics – Gene, Disease, Drug and Placebo Interactions: A Case Study in COMT

“…Still, recent meta-analyses reported a COMT association with AD among Asians but not Caucasians [45] Autoimmune disease COMT's role in limiting the damaging effects of oxidative and emotional stress make its potential role in the etiology of auto-immune diseases plausible. Studies in psoriasis, narcolepsy and systemic lupus erythematosus suggest a link between COMT and autoimmune diseases [46][47] Cardiometabolic disease…”

“…COMT's role in limiting the damaging effects of oxidative and emotional stress also make its potential role in the etiology of auto-immune diseases plausible [46]. Studies in psoriasis [67], narcolepsy [68], and systemic lupus erythematosus [47,69] support this hypothesis, but more work needs to be done in this area.…”

The Role of Genetic Polymorphisms as Related to One-Carbon Metabolism, Vitamin B6, and Gene–Nutrient Interactions in Maintaining Genomic Stability and Cell Viability in Chinese Breast Cancer Patients

“…Our previous study underlines the capacity of the SHMT C1420T polymorphism being able to directly reduce breast cancer risk. [ 14 , 38 ]. The study found risk reduction for the SHMT 1420TT genotype in malignant lymphomas [ 39 ], adult acute lymphocytic leukemia [ 40 ], and also in a wide spectrum of diseases including Parkinson’s disease (PD), coronary artery disease (CAD) and systemic lupus erythematosus (SLE) [ 38 ].…”

“…[ 14 , 38 ]. The study found risk reduction for the SHMT 1420TT genotype in malignant lymphomas [ 39 ], adult acute lymphocytic leukemia [ 40 ], and also in a wide spectrum of diseases including Parkinson’s disease (PD), coronary artery disease (CAD) and systemic lupus erythematosus (SLE) [ 38 ]. These suggested that the reduction of DNA damage in the SHMT 1420TT genotype might be the main reason for the risk reduction of different cancers and a wide spectrum of diseases.…”

Сontribution of Polymorphic Variation of Тp53 and Xrcc1 Genes to the Susceptibility to Breast Cancer for Women of Kyrgyz and Belarusian Nationality - A Comparative Study on Multifactor Dimensionality Reduction Methods

“…метод MDR активно используется для описания взаимодействий неаллельных генов для различных мультифакториальных патологий: рмЖ [9,15,24], рак легкого [16,19], диабет [26,31], артериальная гипертензия [10,14] и др.…”