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Study of CYP2D6 gene in children with autoimmune hepatitis and P450 IID6 autoantibodies

Cytochrome P450 IID6 is an autoantigen recognized by the sera of children affected with a subtype of autoimmune hepatitis. It was hypothesized that a mutation in the CYP2D6 gene could explain the autoimmune response in these patients. To examine this question, genomic DNA from peripheral lymphocytes (n= 9) and liver (n=l) of 10 patients with anti‐LKM‐l antibody was analysed by Southern blot for genetic association studies between a particular CYP2D6 haplotypc and autoimmune hepatitis. In addition, a region of CYP2D6. from the same genomic DNA. was amplified by polymcrasc chain reaction (PCR) and digested by BstNI, in a search for the most prevalent 29B mutation, described in subjects who do not express the P45O IID6. Total RNA and proteins, prepared from the liver of an anti‐LKM‐l+ patient, were analysed by Northern and Western (immunoblot) blots respectively. Our results do not reveal any major structural change in the DNA of this patient at the CYP2D6 locus that could explain their autoimmune response. Corroborating this observation, no changes were noted either in P450 IID6 mRNA size or in the corresponding protein. However, these data do not exclude the possibility of subtle changes in the protein due to point mutations in critical regions that might trigger an autoimmune response.