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

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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.

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Abbreviations

GCPII:

Glutamate carboxypeptidase II

RFC1:

Reduced folate carrier1

cSHMT:

Cytosolic serine hydroxy methyltransferase

TYMS:

Thymidylate synthase

MTHFR:

Methylene tetrahydrofolate reductase

MTR:

5-Methyltetrahydrofolate-homocysteine methyltransferase

MTRR:

5-Methyltetrahydrofolate-homocysteine methyltransferase reductase

SAM:

S-adenosyl methionine

SAH:

S-adenosyl homocysteiene

CYP1A1:

Cytochrome P450

GST:

Glutathione-S-transferase

COMT:

Catecholamine-O-methyl transferase

MDR:

Multifactor dimensionality reduction analysis

SLE:

Systemic lupus erythematosus

CAD:

Coronary artery disease

PD:

Parkinson’s disease

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Acknowledgments

This work was supported by two ad hoc research projects funded by Indian council of Medical Research, New Delhi (Ref No. 5/13/32/2007 and Ref No. 61/12/2010-BMS) and Prof. T. R. Rajagopalan Research Fund of SASTRA University, Thanjavur, India.

Conflicts of interest

All the authors herewith declare no conflicts of interest.

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Authors and Affiliations

  1. School of Chemical and Biotechnology, SASTRA University, Tirumalaisamudram, Thanjavur, 613401, India

    Shaik Mohammad Naushad, Sampathkumar Sowganthika, M. Janaki Ramaiah & Dunna Nageswara rao

  2. Department of Clinical Pharmacology & Therapeutics, Nizam’s Institute of Medical Sciences, Panjagutta, Hyderabad, 500082, India

    Sana Venkata Vijayalakshmi, Yedluri Rupasree & Vijay Kumar Kutala

  3. Centre for Biotechnology, Jawaharlal Nehru Technological University, Hyderabad, 500085, India

    Nadella Kumudini

  4. Gastrocare Hospital, Trichy, 620018, India

    Janardhanan Venketlakshmi Naidu

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  1. Shaik Mohammad Naushad
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Naushad, S.M., Vijayalakshmi, S.V., Rupasree, Y. et al. Multifactor dimensionality reduction analysis to elucidate the cross-talk between one-carbon and xenobiotic metabolic pathways in multi-disease models. Mol Biol Rep 42, 1211–1224 (2015). https://doi.org/10.1007/s11033-015-3856-z

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