It has been suggested that Neel's ''thrifty genotype'' model may account for high body weights in some Oceanic populations, which presumably arose in modern times. In European populations, common variants (rs1421085-C, rs17817449-G, and rs9939609-A) in the fat mass and obesity (FTO associated) were recently found to be associated with body mass index (BMI) or obesity. In this study, we investigated the population frequencies of these variants in six Oceanic populations (Melanesians, Micronesians, and Polynesians) and tested for an association with BMI. Unlike European populations, the Oceanic populations displayed no significant association between the FTO polymorphisms and BMI. These variants were in strong linkage disequilibrium. The population frequencies ranged between 4.2 and 30.3% in the six Oceanic populations, and were similar to those in southeast and east Asian populations. Our study of the FTO polymorphisms has generated no evidence to support the thrifty genotype hypothesis for Oceanic populations.

The hemoglobin E variant (HbE; ( beta )26Glu-->Lys) is concentrated in parts of Southeast Asia where malaria is endemic, and HbE carrier status has been shown to confer some protection against Plasmodium falciparum malaria. To examine the effect of natural selection on the pattern of linkage disequilibrium (LD) and to infer the evolutionary history of the HbE variant, we analyzed biallelic markers surrounding the HbE variant in a Thai population. Pairwise LD analysis of HbE and 43 surrounding biallelic markers revealed LD of HbE extending beyond 100 kb, whereas no LD was observed between non-HbE variants and the same markers. The inferred haplotype network suggests a single origin of the HbE variant in the Thai population. Forward-in-time computer simulations under a variety of selection models indicate that the HbE variant arose 1,240-4,440 years ago. These results support the conjecture that the HbE mutation occurred recently, and the allele frequency has increased rapidly. Our study provides another clear demonstration that a high-resolution LD map across the human genome can detect recent variants that have been subjected to positive selection.

The mechanisms underlying severe thrombocytopenia in dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) are not completely understood. We present here the first evidence that dengue type 2 virus binds to human platelets only in the presence of virus-specific antibody, supporting a role for immune-mediated clearance of platelets in the pathogenesis of thrombocytopenia in DHF/DSS. Antibody-enhanced binding of virus of platelets was also demonstrated with a panel of eight murine monoclonal antibodies specific for the dengue E protein. The degree of binding was dependent on the antibody used but not on the antibody IgG subclass, indicating that factors other than the platelet Fc receptor are involved in binding of virus-antibody complexes to the platelet surface. Confirmation that antibody-dependent virus binding to platelets is not primarily mediated by the platelet Fc receptor was obtained by demonstrating good binding even when platelets were pretreated with the Fc gamma RII-specific antibody IV.3.