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OBJECTIVE: To characterize, among European and Han Chinese populations, the genetic predictors of maculopapular exanthema (MPE), a cutaneous adverse drug reaction common to antiepileptic drugs. METHODS: We conducted a case-control genome-wide association study of autosomal genotypes, including Class I and II human leukocyte antigen (HLA) alleles, in 323 cases and 1,321 drug-tolerant controls from epilepsy cohorts of northern European and Han Chinese descent. Results from each cohort were meta-analyzed. RESULTS: We report an association between a rare variant in the complement factor H-related 4 (CFHR4) gene and phenytoin-induced MPE in Europeans (p = 4.5 x 10(-11); odds ratio [95% confidence interval] 7 [3.2-16]). This variant is in complete linkage disequilibrium with a missense variant (N1050Y) in the complement factor H (CFH) gene. In addition, our results reinforce the association between HLA-A*31:01 and carbamazepine hypersensitivity. We did not identify significant genetic associations with MPE among Han Chinese patients. CONCLUSIONS: The identification of genetic predictors of MPE in CFHR4 and CFH, members of the complement factor H-related protein family, suggest a new link between regulation of the complement system alternative pathway and phenytoin-induced hypersensitivity in European-ancestral patients.

OBJECTIVE: To characterize, among European and Han Chinese populations, the genetic predictors of maculopapular exanthema (MPE), a cutaneous adverse drug reaction common to antiepileptic drugs. METHODS: We conducted a case-control genome-wide association study of autosomal genotypes, including Class I and II human leukocyte antigen (HLA) alleles, in 323 cases and 1,321 drug-tolerant controls from epilepsy cohorts of northern European and Han Chinese descent. Results from each cohort were meta-analyzed. RESULTS: We report an association between a rare variant in the complement factor H-related 4 (CFHR4) gene and phenytoin-induced MPE in Europeans (p = 4.5 x 10(-11); odds ratio [95% confidence interval] 7 [3.2-16]). This variant is in complete linkage disequilibrium with a missense variant (N1050Y) in the complement factor H (CFH) gene. In addition, our results reinforce the association between HLA-A*31:01 and carbamazepine hypersensitivity. We did not identify significant genetic associations with MPE among Han Chinese patients. CONCLUSIONS: The identification of genetic predictors of MPE in CFHR4 and CFH, members of the complement factor H-related protein family, suggest a new link between regulation of the complement system alternative pathway and phenytoin-induced hypersensitivity in European-ancestral patients.

In recent years, food safety has become a very important issue in Hong Kong and Mainland China, especially after the discovery of contamination of milk products by melamine and the contamination of seafood by malachite green. The Hong Kong government regulates the presence of harmful substances in food through Ordinance Cap.132AF HARMFUL SUBSTANCES IN FOOD REGULATIONS and Cap.139N PUBLIC HEALTH (ANIMALS AND BIRDS) (CHEMICAL RESIDUES) REGULATION. Approximately 50 chemicals are listed, including antibiotics, synthetic hormones and some harmful chemicals. The Hong Kong government has instituted a system of monitoring the residue levels of these banned substances in food products using liquid chromatography–mass spectrometry and gas chromatography–mass spectrometry. These techniques are highly sensitive, but are time-consuming and only capable of testing limited quantities of food samples. There is an urgent need for a rapid and reliable detection system that can detect such banned substances in larger quantities. This project will develop an immunoassay-based detection system for the rapid detection of residues in food animal products. The chemicals, enrofloxacin, tylosin and malachite green are the chosen targets for detection. Conjugation of these chemicals to protein carriers was conducted and the resultant conjugates were injected into animals for antibody production. Specific antibodies were purified and finally incorporated into the detection systems.

In recent years, food safety has become a very important issue in Hong Kong and Mainland China, especially after the discovery of contamination of milk products by melamine and the contamination of seafood by malachite green. The Hong Kong government regulates the presence of harmful substances in food through Ordinance Cap.132AF HARMFUL SUBSTANCES IN FOOD REGULATIONS and Cap.139N PUBLIC HEALTH (ANIMALS AND BIRDS) (CHEMICAL RESIDUES) REGULATION. Approximately 50 chemicals are listed, including antibiotics, synthetic hormones and some harmful chemicals. The Hong Kong government has instituted a system of monitoring the residue levels of these banned substances in food products using liquid chromatography–mass spectrometry and gas chromatography–mass spectrometry. These techniques are highly sensitive, but are time-consuming and only capable of testing limited quantities of food samples. There is an urgent need for a rapid and reliable detection system that can detect such banned substances in larger quantities. This project will develop an immunoassay-based detection system for the rapid detection of residues in food animal products. The chemicals, enrofloxacin, tylosin and malachite green are the chosen targets for detection. Conjugation of these chemicals to protein carriers was conducted and the resultant conjugates were injected into animals for antibody production. Specific antibodies were purified and finally incorporated into the detection systems.