ABSTRACT:Cyp3A5 activity varies within any given ethnic population, suggesting that genetic variation within the Cyp3A5 gene may be the most important contributor to interindividual and interracial differences in Cyp3A-dependent drug clearance and response. The full extent of Cyp3A5 polymorphism in a white and an indigenous African population was analyzed using DNA direct sequencing procedures. The presence of 10 and 12 single nucleotide polymorphisms was detected in the white and African samples, respectively. Thirteen novel mutations occurring at low frequencies were identified in these populations. Significant differences were observed in the distribution of Cyp3A5*3, Cyp3A5*6, and Cyp3A5*7 alleles among white and African populations. The frequency of Cyp3A5*3 allele in white Canadians (ϳ93%) is higher than in Zimbabweans (77.6%) (p < 0.001). In contrast, Cyp3A5*6 and Cyp3A5*7 alleles are relatively frequent in African subjects (10-22%) but absent in white subjects (p < 0.001). These differences may reflect evolutionary pressures generated by environmental factors in geographically distinct regions. However, the genetic polymorphism of Cyp3A5 alone does not explain the interindividual differences in Cyp3A-mediated metabolism.

The complete absence of Cyp3A5*3 allele and the accumulation of less than three copies of MDR-1 (T-129C, C3435T and G2677T) polymorphisms are associated with lower tacrolimus blood levels identifying these genotypes as markers for patients requiring higher tacrolimus doses.

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HIV infection is associated with immune dysregulation primarily affecting T-cell function, whereas asthma is related to excessive T-cell activity. We compared the prevalence of asthma and related conditions among adult seropositive men with the prevalence among men of similar age drawn from the general population. Seropositive men had a significantly more frequent occurrence of wheezing (54.4 versus 21.2%), bronchial hyperresponsiveness (BHR) to methacholine (26.2 versus 14.4%), and an elevated total serum IgE (37.8 versus 25.7%). Differences in BHR were significant only among smokers. Among the seropositive men, FEV(1)/FVC and an elevated IgE were the principal determinants of BHR. Our results suggest that the frequency of asthma may be underestimated in HIV disease. Furthermore, the frequent occurrence of BHR in HIV-infected men who smoke (30.1%) suggests this group may be especially susceptible to the adverse effects of cigarette smoke.

EBV-associated LPD may range from benign lymphoid hyperplasia to high-grade lymphoma. The most common CT manifestation consists of multiple nodules, frequently in a predominantly peribronchovascular or subpleural distribution.