Cytochrome (CYP) P450 2E1 is clinically and toxicologically important and it is constitutively expressed in the liver and many other tissues. In contrast to many other CYP isoenzymes, indisputable evidence for a functionally important polymorphism of CYP2E1 in the human population is lacking. CYP2E1 metabolizes a wide variety of chemicals with different structures, in particular small and hydrophobic compounds, including potential cytotoxic and carcinogenic agents. In addition, chlorzoxazone and trimethadione metabolism are good CYP2E1 probes for liver disease in vivo and in vitro. In the future, methods for fully analysing the function of CYP2E1 using knockout mice will be established. This article reviews recent advances in our understanding of the role of human CYP2E1 in drug metabolism.

A homozygous gene deletion at the GST1 locus of genomic DNA isolated from peripheral blood was investigated for its relationship with several types of cancer using the polymerase chain reaction (PCR) technique. DNA samples were prepared from blood obtained from 128 healthy blood donors and 150 patients with cancer or chronic hepatitis. PCR primers were prepared based on the human cDNA sequence and the intron/exon sequences of the rat Yb2 gene. The amplified sequence between exons 5 and 6 including intron 5 showed very clearly the presence of absence of the GST1 gene, after electrophoresis in a 2% agarose gel. Segregation of the presence and absence of PCR product from samples of twins and their parents indicated that presence involves homozygous or heterozygous normal GST1 genotypes while absence involves only homozygous gene deletion. The patients with stomach cancer had a significantly higher frequency of gene deletion than did the healthy controls (P < 0.005). Thus, GST1 deletion may be a possible genetic marker for early detection of a group at high risk of stomach cancer.

The molecular basis and biochemical mediators of genetic growth propensity and adult height achievement in the general population are largely unknown. Pygmies represent one extreme of the height spectrum that may provide important clues regarding this issue. Previous studies in pygmies from Africa and Papua-New Guinea have shown decreased serum levels of growth hormone binding protein (GHBP), the circulating ectodomain of the growth hormone receptor (GHR). By inference, a similar limitation in tissue GHR expression has been assumed to be responsible for the partial growth hormone (GH) resistance observed in African pygmies. It is not clear how generalizable this concept is to other populations. To address this question, we studied two pygmy populations from the Philippines (Aeta and Mamanwa people) that are unrelated to the African pygmies. Serum GHBP and IGF-I levels were significantly decreased in both pygmy populations, compared to normal-statured Philippino controls. The results, together with previous observations in African and New Guinean pygmies, indicate that short stature is associated with low serum GHBP levels in pygmy populations of diverse origins and in different parts of the world. This strengthens the tentative postulate that the GHBP/GHR system plays an important role in the genetic and perhaps nutritional determination of adult stature in humans. Molecular genetic studies of the GHR gene in various pygmy populations may shed further light on the mystery of pygmy short stature.

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SummaryPolymorphism of the seventh component of human complement (C7) was investigated in Japanese. Four common and one rare allotypes were observed with desialized samples. Besides three common alleles, C7"1, C7"2 and C7"4, the existence of the hypomorphic variant, C7"3, was confirmed in Japanese with a polymorphic frequency. The recently described C7"5 was found to correspond to C7"3 by comparing with reference samples. Moreover, a rare variant, tentatively named C7 7, was considered to be new. The population samples were also typed for C6. A rare variant, designated M92, was newly found. No significant associations between C6 and C7 alleles were found.

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