Epigenetics and Nutrition in α-1 Antitrypsin Deficiency

Abstract

Alpha-1 proteinase inhibitor (PI), also known as alpha-1 antitrypsin (AAT), is the most abundant circulating serine protease inhibitor (serpin) and the prototypical member of the serpin superfamily. AAT primarily inhibits neutrophil elastase (NE) instead of trypsin. Mutations occurring in the gene encoding AAT lead to AAT deficiency (AATD). Patients with AATD are susceptible to emphysema, COPD, liver failure, and less commonly, systemic anti-neutrophil cytoplasmic antibody (ANCA)-positive vasculitis and necrotizing panniculitis. Single nucleotide polymorphisms (SNPs), DNA methylation, altered microRNA (miRNA) expression, and various epigenetic factors, including mRNA isoforms of the SERPINA1 gene, have known or potential direct effects on the clinical manifestation of AATD. Dietary patterns influence epigenetic mechanisms. Therefore, it may be possible to modify the progression of respiratory and liver diseases associated with AATD through nutritional strategies.

Keywords

• α-1 antitrypsin
• epigenetic
• COPD
• liver failure

α-1 Antitripsin Eksikliğinde Epigenetik ve Beslenme

Abstract

α-1-proteinaz inhibitörü (PI) olarak da bilinen α-1 antitripsin (AAT), dolaşımdaki en bol serin proteaz inhibitörüdür (serpin) ve serpin süper ailesinin prototipik üyesidir. AAT, tripsin yerine birincil olarak nötrofil elastazını (NE) inhibe eder. AAT kodlayan gen üzerinde de meydana gelen mutasyonlar sonucunda AAT eksikliği (AATD) meydana gelmektedir. AATD'li hastalar amfizem, Kronik obstrüktif akciğer hastalığı (KOAH), karaciğer yetmezliği ve daha az yaygın olarak sistemik anti-nötrofil sitoplazmik antikor (ANCA)-pozitif vaskülit ve nekrotizan pannikülite karşı hassastır. Tek nükleotid polimorfizmleri (TNP'ler), DNA metilasyonu, değiştirilmiş mikroRNA (miRNA) ekspresyonu ve SERPINA1 geni mRNA izoformları dahil olmak üzere çok sayıda epigenetik faktörün AATD'nin klinik görünümü üzerinde bilinen veya olası doğrudan etkileri vardır. Beslenme şekli epigenetik mekanizmaları etkilemektedir. Dolayısıyla AATD’ye bağlı gelişen solunum yolu ve karaciğer hastalıklarının progrozunu beslenme stratejileriyle değiştirmek mümkün olabilir.

Keywords

• α-1 antitipsin
• epigenetik
• KOAH
• karaciğer yetmezliği

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