JPET #133306
Legends for Supplemental Figures
Supplemental Figure 1. Histogram of CYP2B6 mRNA expression (β-actin normalized) in 150 human liver samples. The inset shows median mRNA levels stratified according to gender and several life style factors including smoking and frequent intake of alcohol, coffee and grapefruit juice as documented by a questionnaire.
Supplemental Figure 2: Histogram of CYP2B6 protein expression in 235 liver samples. The inset shows median protein levels stratified according to gender and several life style factors including smoking and frequent intake of alcohol, coffee and grapefruit juice as documented by a questionnaire.
Supplemental Figure 3. Histogram of microsomal bupropion (50 µM) hydroxylase activity in 235 liver samples. The insert shows median activity levels stratified according to gender and several life style factors including smoking and frequent intake of alcohol, coffee and grapefruit juice as documented by a questionnaire.
Supplemental Figure 4: Correlation analysis in 150 human liver samples
A: Correlation between microsomal CYP2B6 protein and mRNA (β-actin normalized)
B.: Correlation between microsomal bupropion (50 µM) hydroxylase activity and CYP2B6 protein. Spearman rank correlation coefficient rS was calculated between CYP2B6 mRNA and protein (rs=0.41, p<0.0001) as well as between protein and bupropion hydroxylase activity (rs=0.59, p<0.0001).
Supplemental Figure 5. Relationship between genotype and CYP2B6 protein expression, microsomal bupropion (50 µM) hydroxylase activity or specific activity in human liver samples.
A: Scatterplots depicting CYP2B6 protein expression derived from western blot analysis shown in pmol/mg microsomal protein for various genotypes.
B: Microsomal bupropion (50 µM) hydroxylase activity as a marker for CYP2B6 activity in relation to various genotypes.
C: Specific activity calculated as microsomal activity divided by specific CYP2B6 protein content within each liver sample in relation to various genotypes. Some genotype groups are not shown due to insufficient number of individuals. Statistical significance is indicated by brackets pointing at the two groups compared by Mann-Whitney test.
Supplemental Figure 6. Compilation of transcript variants of CYP2B6
Shaded boxes represent exonic and white boxes intronic sequences. If possible, nomenclature of spliced transcripts was used as described before (Miles at. al 1989 and Lamba et. al. 2003). SV6 was newly designated and SV7 and SV8 are novel splice variants not described before.
Gene numbering was according to general guidelines with the A of the ATG initiation codon of CYP2B6 set as +1.
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