Thymidylate synthase (TS) catalyses the conversion of deoxy-uridylate to deoxy-thymidylate and is essential for DNA synthesis. Pullarkat et al (pages 65–70) tested 50 patients with disseminated colorectal cancer who received 5-FU treatment to determine whether the thymidylate synthase polymorphism will predict clinical outcome. They found that individuals with the double (short) repeat variant genotype had a response rate of 50% when compared to 9% in those with the triple (long) repeat variant and 15% in with the heterozygous genotype. It also indicates that patients with the triple repeat variant had less severe side effects to 5-FU. The data suggest that genotyping for the TS polymorphism may have the potential to identify patients more likely to respond to 5-FU based chemotherapy.
Fukushima et al (pages 78–83) have analyzed the functional significance of G649 and report an allelic variant in the human H2 receptor which confers altered receptor function. The variant receptor has been associated with markedly lower basal cAMP productions than the wild-type receptor, while histamine-dependent cAMP productions via the variant receptor have been lower as well. They analyzed gastric acid secretion in 100 Japanese control subjects with this variant, but neither heterozygotes nor homozygotes were found, suggesting that this variant is uncommon in the Japanese population. In contrast, previous studies in the British population have shown that this variant exists in Europe and that it is associated with schizophrenia.
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