THE LANCET 922 Vol 349 • March 29, 1997 there are known racial differences in the frequencies of the PM phenotype: about 3% of whites and in 13–23% of orientals. 3 Poor metabolism results from a defect in the gene associated with the cytochrome P450 isoenzyme, CYP2C19. Two genetic defects, m1 and m2, have been identified: the former accounts for 75–83% of the defective alleles in both white and Japanese PMs, while the latter was found only in Japanese. 4 We determined the distribution of the two CYP2C19 mutations in two Vanuatu islands. In March, 1996, malariometric surveys were conducted on Tanna and Malakula islands. The survey included finger prick sampling of blood for PCR from a capillary tube (75 μL) on to a filter paper. Dried filter-paper samples were collected from 493 people. DNA was extracted from a quarter of a dried blood spot. PCR was conducted as described by de Morais et al, 4 with PCR amplification of exon 5 followed by Sma1 digestion (CYP2C19m1) and amplification of exon 4 followed by BamH1 digestion (CYP2C19m2). The genotypes of the 493 villagers are shown in the table. Remarkably high frequencies of the two mutations were found. The overall frequency of the m1 alleles was 0·708 (698/986), and that of the m2 alleles was 0·133 (131/986). Only 145 individuals had at least one wild-type allele (wt). The observed genotype distribution corresponded well with those estimated from the allele frequencies of CYP2C19m1 and m2 in the study group, in accordance with a Hardy- Weinberg equilibrium ( 2 -test, p>0·5, power >99%). The population of Tanna Island showed higher frequency of m1 and lower frequency of m2 than that of Malakula Island (p<0·05). In a separate study we correlated proguanil and cycloguanil concentration profiles in whole blood with genotypes in patients with malaria from the same area (unpublished). The results confirm that the genotyping predicted the phenotypes in all 20 patients tested. Thus, the data in the table suggest that 348 (70·6%) individuals have PM phenotype, which may have major implications for the efficacy of proguanil in this population. CYP2C19 is also involved in the metabolism of other drugs such as imipramine, omeprazole, and diazepam. 3 Anthropological evidences suggest that Melanesians are of Mongoloid origin, and the ancestors of the people in Vanuatu may have migrated from Papua New Guinea about 4000 years ago. 5 Therefore, the finding of m2 mutation in Vanuatu is not surprising. However the reasons for the high frequency of the m1 allele are unclear. 1 Radloff PD, Philipps J, Nkeyi M, Hutchinson D, Kremsner PG. Atovaquone and proguanil for Plasmodium falciparum malaria. Lancet 1996; 347: 1511–14. 2 Ward SA, Helsby NA, Skjelbo E, Brosen K, Gram LF, Breckenridge AM. The activation of the biguanide antimalarial proguanil co-segregates with the mephenytoin oxidation polymorphism—a panel study. Br J Clin Pharmacol 1991; 31: 689–92. 3 Bertilsson L. Geographical/interracial differences in polymorphic drug oxidation. Clin Pharmacokinet 1995; 29: 192–209. 4 de Morais SMF, Wilkinson GR, Blaisdell J, Meyer UA, Nakamura K, Goldstein JA. Identification of a new genetic defect responsible for the polymorphism of (S)-mephenytoin metabolism in Japanese. Mol Pharmacol 1994; 46: 594–98. 5 Katayama K. A scenario on prehistoric Mongoloid dispersals into the South Pacific, with special reference to hypothetic proto-oceanic connection. Man Culture Oceania 1990; 6: 151–59. Department of International Affairs and Tropical Medicine, Tokyo Women’s Medical College, Tokyo 162, Japan (A Kaneko) ; Department of Medical Zoology, Osaka City University School of Medicine, Osaka; Malaria Section, Department of Health, Port Vila, Vanuatu; and Division of Infectious Diseases, Karolinska Institutet Danderyd Hospital, Stockholm, Sweden Island Number of people Number of individuals with respective genotype* Frequency of mutant allele wt/wt wt/m1 wt/m2 m1/m2 m1/m1 m2/m2 m1 m2 Tanna 266 6 60 6 46 144 4 0·741 0·113 Malakula 227 6 49 18 49 103 2 0·670 0·156 Total observed 493 12 109 24 95 247 6 0·708§ 0·133‡ Total estimated† 493 12 111 21 93 247 9‡ *wt =wild type allele, m1=CYP2C19m1 allele, m2=CYP2C19m2 allele. †Calculated from the observed allele frequencies of m1 and m2, in accordance with a Hardy-Weinberg equilibirum. §95% confidence interval=0·680 to 0·763. ‡95% confidence interval=0·112 to 0·154. Frequencies of CYP2C19 mutant alleles in two islands of Vanuatu 32 bp CCR-5 gene deletion and resistance to fast progression in HIV-1 infected heterozygotes Jay Rappaport, Yi-Yun Cho, Houria Hendel, Elissa J Schwartz, François Schachter, Jean-François Zagury Chemokine and AIDS research fields are converging. CCR-5 and fusin are receptors for chemokines which have been recently identified as co-receptors for HIV-1 infection. The CC-chemokines MIP-1, MIP-1, and Rantes bind to the CCR-5 receptor and can inhibit infection of target cells by HIV-1 monocytotropic strains. 1 A 32 base-pair deletion in the CCR-5 gene (32) is present in approximately 18% of white people, but virtually absent in black and Asian people. People homozygous for the 32 deletion are resistant to HIV infection. 2–4 Among heterozygotes, this deletion does not seem to confer resistance to HIV-1 infection. The role of the mutant CCR-5 allele in late disease progression is not yet clear. 4 To gain insight into the role of CCR-5 in disease progression, we studied CCR-5 allele frequencies in HIV-1 infected individuals from the GRIV cohort which gathers blood samples from people in France characterised as either rapid or slow progressors. The GRIV cohort is the largest collection of blood samples from slow/fast progressors to-date (survey of more than 10 000 patients 5 ). The people were selected by focusing on the extremes of clinical outcome in order to increase the significance of genetic analysis. Slow progressors were defined as HIV-infected people without symptoms for more than 8 years with CD4 cell count above 50010 6 /L in the absence of antiretroviral therapy. Fast progressors were those who had a CD4 cell count below 30010 6 /L less than 3 years after seroconversion. With experimental methods previously published, 2 we evaluated the prevalence of the mutant allele of CCR-5 in 34 fast and 66 slow progressors. The prevalence of 32 deletion (heterozygous) among slow progressors was 24·3% (16/66) and among fast progressors was 2·9% (1/34). These results suggest that CCR-5 heterozygosity protects individuals from progression early after infection (p<0·05). The enrichment for the 32 allele among slow progressors (24% versus an expected 18% in the general white population) did not reach statistical significance. Of interest, the 16 heterozygous slow progressor individuals did not seem to have been preferentially infected by a specific route (hetero/homosexual, drug, transfusion).