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Idiopathic pulmonary fibrosis and polymorphisms of the folate pathway genes

Authors:	Marcella Martinelli Luca Scapoli Paolo Carbonara Ilaria Valentini Ambra Girardi Francesca Farinella Gabriella Mattei Angela Maria Grazia Pacilli Luca Fasano Stefano Nava Rossella Solmi

Institution:	1. Dipartimento di Istologia, Embriologia e Biologia Applicata, Università di Bologna, Via Belmeloro 8, 40126 Bologna, Italy;2. Centro di Ricerca in Genetica Molecolare “Fondazione CARISBO,” Bologna, Italy;3. Dipartimento di Medicina Interna dell''Invecchiamento e Malattie Nefrologiche, Università di Bologna, via Massarenti, 9, 40138 Bologna, Italy;4. Dipartimento di Discipline Medico Chirurgiche della Comunicazione e del Comportamento, Corso Giovecca 203, 44121 Ferrara, Italy;5. Dipartimento Cardio-Toraco-Vascolare, UO Pneumologia e TI Respiratoria, Policlinico S.Orsola-Malpighi, via Massarenti, 9, 40138 Bologna, Italy;1. Bronx-Lebanon Hospital Center, Bronx, New York;2. University of Pennsylvania, Philadelphia, Philadelphia;3. Johns Hopkins University, Baltimore, Maryland;1. Department of Veterinary Pathology, Faculty of Veterinary Medicine, Kafr El-Sheikh University, Kafr El-Sheikh, Egypt;2. Department of Veterinary Pathology, Faculty of Veterinary Medicine, Beni-Suef University, Egypt;3. Department of Pathogenetic Veterinary Sciences, United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan;4. Department of Pathology and Clinical Pathology, Faculty of Veterinary Medicine, South Valley University, Qena 83523, Egypt;6. Department of Animal Medicine and Infectious Diseases, Faculty of Veterinary Medicine, Sadat City University, Sadat City 32897, Egypt;5. Department of Poultry and Rabbit Medicine, Faculty of Veterinary Medicine, Suez Canal University, Egypt;1. Department of Pharmacy, Qilu Hospital, Shandong University, Jinan, China;2. School of Pharmacy, Shandong University, Jinan, China;3. Department of Emergency, Qilu Hospital of Shandong University, Jinan, China;4. Minimally Invasive Urology Center, Provincial Hospital Affiliated to Shandong University, Jinan, China

Abstract:	ObjectivesThis study aims to determine the possible association between folate pathway gene polymorphisms and idiopathic pulmonary fibrosis. This represents the first study carried out on folate pathway gene polymorphisms as possible risk factors in this kind of pathology. The premise is that several polymorphisms mapping on genes responsible for folate uptake are associated with the risk of numerous diseases occurring between pregnancy and old age, and that too little is currently known about idiopathic pulmonary fibrosis.Design and methodsWe genotyped 9 single nucleotide polymorphisms and 1 polymorphic insertion in 7 essential genes belonging to the folate pathway in 32 Italian idiopathic pulmonary fibrosis patients and 81 control subjects. This was done by PCR and restriction analysis.ResultsAllelic and genotypic association tests indicated that for all the analysed polymorphisms there were no significant differences between patients and controls. Nevertheless, the haplotype association analysis revealed a significant association between idiopathic pulmonary fibrosis and transcobalamin II gene polymorphisms: specifically the haplotype 776G (rs1801198)–c.1026-394G (rs7286680)–444C (rs10418) (OR = 2.84; 95% C.I. 1.36–5.93, P value = 0.004).ConclusionsThis small-scale preliminary study would suggest the importance of further research focusing on the role of folate in the onset of idiopathic pulmonary fibrosis.

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