CYP2D6*36 gene arrangements within the cyp2d6 locus: association of CYP2D6*36 with poor metabolizer status.

Unexplained cases of CYP2D6 genotype/phenotype discordance continue to be discovered. In previous studies, several African Americans with a poor metabolizer phenotype carried the reduced function CYP2D6*10 allele in combination with a nonfunctional allele. We pursued the possibility that these alleles harbor either a known sequence variation (i.e., CYP2D6*36 carrying a gene conversion in exon 9 along the CYP2D6*10-defining 100C>T single-nucleotide polymorphism) or novel sequences variation(s). Discordant cases were evaluated by long-range polymerase chain reaction (PCR) to test for gene rearrangement events, and a 6.6-kilobase pair PCR product encompassing the CYP2D6 gene was cloned and entirely sequenced. Thereafter, allele frequencies were determined in different study populations comprising whites, African Americans, and Asians. Analyses covering the CYP2D7 to 2D6 gene region established that CYP2D6*36 did not only exist as a gene duplication (CYP2D6*36x2) or in tandem with *10 (CYP2D6*36+*10), as previously reported, but also by itself. This "single" CYP2D6*36 allele was found in nine African Americans and one Asian, but was absent in the whites tested. Ultimately, the presence of CYP2D6*36 resolved genotype/phenotype discordance in three cases. We also discovered an exon 9 conversion-positive CYP2D6*4 gene in a duplication arrangement (CYP2D6*4Nx2) and a CYP2D6*4 allele lacking 100C>T (CYP2D6*4M) in two white subjects. The discovery of an allele that carries only one CYP2D6*36 gene copy provides unequivocal evidence that both CYP2D6*36 and *36x2 are associated with a poor metabolizer phenotype. Given a combined frequency of between 0.5 and 3% in African Americans and Asians, genotyping for CYP2D6*36 should improve the accuracy of genotype-based phenotype prediction in these populations.     

Pulmonary nodules studied by computed tomography

The authors analyzed 177 pulmonary nodules using thin-section computed tomography (CT), calculating the representative CT number (RCT#) from a computer printout. None of the 96 malignant nodules had an RCT# greater than 151 H. Of the 81 benign nodules, 14 were shown to be calcified by conventional radiography and had an RCT# ranging from 763 and 1,023 H. Thirty had an RCT# greater than 200 H; this included 24 which showed no calcification on conventional tomograms. The remaining 37 benign nodules had an RCT# less than 200 H; 6 of them were hamartomas, including 2 which were diagnosed as such due to their fat content.     

Cigarette smoking and drug use in schoolchildren: IV--factors associated with changes in smoking behaviour

Factors associated with changes in the smoking behaviour of approximately 6000 schoolchildren (two cohorts aged between 10 and 12 years in 1979) over 12 months are described. They were measured twice as part of a randomized controlled trial of a smoking prevention programme. Four groups were defined: (a) those who became smokers (adopters); (b) those who remained non-smokers; (c) those who became non-smokers (quitters), and, (d) those who remained smokers. Personal and social variables were ordered using a logistic regression model according to the strength of their association with adopting and quitting smoking. Factors distinguishing adopters from children who remained nonsmokers were, being a member of the older cohort, having friends who smoke, having siblings who smoke, approving of cigarette advertising and having a relatively large amount of money to spend each week. Factors distinguishing quitters from children who continued to smoke were, having siblings who do not smoke, being a member of the younger cohort, disapproving of cigarette advertising and having a relatively small amount of money to spend each week. Initial attitude scores were indicative of future smoking behaviour and where smoking behaviour changed, attitudes also changed so that the two remained congruent. The younger cohort improved their knowledge of smoking hazards over the year irrespective of their smoking behaviour. The older cohort showed significant differences in knowledge which were dependent upon smoking category, with 1980 smokers having lower knowledge scores than non-smokers and showing an apparent decrement in their previous knowledge.