Interactions between genes and the environment. Epigenetics in allergy.
Epigenetics is defined as those inheritable changes occurring in gene expression, without actual modification in the genic DNA sequence. Epigenetic factors are chemically stable, potentially reversible, and can be modulated or induced by environmental factors. In the case of allergic disease, epigenetics could explain not only the discordances observed between monozygous twins but also phenomena such as incomplete penetrance, variable expression, gender and progenitor effects, and sporadic cases. In this sense, the hypothesis of hygiene is of great relevance in that it integrates genetic and epidemiological data in the context of environmental exposures. Among the different epigenetic factors, mention must be made of DNA methylation, covalent histone modifications, and other mechanisms that include different protein complexes and RNA-mediated modifications. The regulatory effect of these phenomena upon immune response has important implications for allergic diseases. At present, different lines of pharmacological research are being conducted, based on the modulation of epigenetic factors, modifying expression of the genes that encode for proteins implicated in allergic processes. Among such modulators, mention can be made of antisense oligonucleotides, ribozymes and interference RNA. The applications of epigenetics to the diagnosis and treatment of allergic disorders offer a very promising future of this specialty.
Service of Clinical Biochemistry. Salamanca University Hospital. Salamanca. Spain.
M
M
Isidoro-García
I
I
Dávila-González
M
M
Pascual de Pedro
C
C
Sanz-Lozano
F
F
Lorente-Toledano
D002454:Cell Differentiation / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic / Q000235:genetics* / Q000276:immunology*; D005492:Folic Acid / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D020022:Genetic Predisposition to Disease; D006657:Histones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000178:diet therapy / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology*; D034741:RNA, Small Interfering; D018417:Th1 Cells / Q000502:physiology; D018418:Th2 Cells / Q000502:physiology; D014805:Vitamin B 12 / Q000627:therapeutic use
D006657:Histones; D034741:RNA, Small Interfering; D005492:Folic Acid; D014805:Vitamin B 12