Association study of genetic factors in subjects with delay hypersensitivity reactions to aromatic antiepileptics

• Grant number: 11/22748-1
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2012
• End date: February 28, 2014
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Jorge Elias Kalil Filho
• Grantee: Jorge Elias Kalil Filho
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Aromatic antiepileptics (ACA) are frequently related with adverse reactions. Non-immediate (late) hypersensitivity reactions to these drugs are impredictable and usualy have important morbity and mortality. There are evidences of immunological and genetic involvement in its genesis. It is supose to have association with specific HLA in specific populations. There are genetic variations in immunological markers such as HLA, TNF and HSP70, and enzymatic factors, as CY2C9, have been associated with the possibility of reactions and their severity in different populations.The recognition of haptens originated from the metabolites of the ACA and the triggering of the immune response are dependent on specific HLA molecules. In addition, there is evidence that the irregular metabolism of the drug may be related with hypersensitivity reactions (HR). The CYP2C9 gene is involved in the biotransformation of ACA and its allelic variations results in a reduced enzyme activity may alter the metabolism of these drugs, resulting in a higher risk of HR. We propose an association study with the investigation of two loci of HLA (A and B) and the occurrence of polymorphisms in HLA genes, TNF, HSP70 and CYP2C9 in patients with RH to ACA and controls (tolerant patients and healthy individuals). This would be the first study in the Brazilian population in this way, the ability to anticipate and prevent these reactions by genetic testing may be an important advance in reducing morbidity and mortality, thus moving toward personalized medicine. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

TANNO, LUCIANA KASE; KERR, DANIEL SHIKANAI; DOS SANTOS, BERNARDO; TALIB, LEDA LEME; YAMAGUTI, CELIA; RODRIGUES, HELCIO; GATTAZ, WAGNER FARID; KALIL, JORGE. The Absence of CYP3A5*3 Is a Protective Factor to Anticonvulsants Hypersensitivity Reactions: A Case-Control Study in Brazilian Subjects. PLoS One, v. 10, n. 8, p. 11-pg., 2015-08-20. (11/22748-1)

TANNO, LUCIANA KASE; KERR, DANIEL SHIKANAI; DOS SANTOS, BERNARDO; TALIB, LEDA LEME; YAMAGUTI, CELIA; RODRIGUES, HELCIO; GATTAZ, WAGNER FARID; KALIL, JORGE. The Absence of CYP3A5{*}3 Is a Protective Factor to Anticonvulsants Hypersensitivity Reactions: A Case-Control Study in Brazilian Subjects. PLoS One, v. 10, n. 8, AUG 20 2015. (11/22748-1)