The main aim of this study was to evaluate the effects of Na intake and cardiorespiratory fitness (CRF) on body composition. The study was also intended to assess whether Na intake and/or CRF mediate the genetic susceptibility to obesity. Analyses were performed on a sample of 526 adult participants from the Quebec Family Study for whom a complete data set was available for nutrient and energy intake, CRF and body composition variables. The effects of Na, CRF and their interaction were analysed by comparing sex-specific tertiles using general linear mixed models. In both males and females, we observed a significant effect of Na intake and CRF on all body composition variables. However, in females only, we found that the effect of Na intake on body composition variables varies according to CRF level such that high Na intake was associated with increased body fatness, but only in females with low CRF. This interaction effect remained significant after statistical adjustment for total sugar, fat and energy intake. Using mediation analysis, we also found Na intake and CRF to be significant mediators of the relationship between a polygenic risk score of obesity based on > 500 000 genetic variants and BMI or waist circumference. In conclusion, the current study shows that Na intake influences body composition via mechanisms that interact with aerobic fitness, especially in females. Furthermore, both Na intake and CRF seem to be involved in the expression of the genetic susceptibility to obesity.

The apparent family clustering of avian influenza A/H5N1 has led several groups to postulate the existence of a host genetic influence on susceptibility to A/H5N1, yet the role of host factors on the risk of A/H5N1 disease has received remarkably little attention compared to the efforts focused on viral factors. We examined the epidemiological patterns of human A/H5N1 cases, their possible explanations, and the plausibility of a host genetic effect on susceptibility to A/H5N1 infection. The preponderance of familial clustering of cases and the relative lack of non-familial clusters, the occurrence of related cases separated by time and place, and the paucity of cases in some highly exposed groups such as poultry cullers, are consistent with a host genetic effect. Animal models support the biological plausibility of genetic susceptibility to A/H5N1. Although the evidence is circumstantial, host genetic factors are a parsimonious explanation for the unusual epidemiology of human A/H5N1 cases and warrant further investigation.

Human helminthiases are common in China, especially in rural areas where sanitation conditions are poor. Soil-transmitted helminths (STHs) are predominantly found in the southern provinces. Schistosoma japonicum is also endemic to southern China. Here we review the prevalence of helminth infections and polyparasitism in China, and discuss the interactions between helminth parasites in the co-infected host. It is clear that STHs are more prevalent in rural China than previously suggested emphasizing the need for systematic control of STHs. Further, the need for improved sanitation and hygiene conditions to prevent parasite transmission is highlighted. We provide supporting evidence for human genetic susceptibility to both single helminth infection and polyparasitism, and suggest that susceptibility to helminths infections may not be independent of one or the other. We demonstrate an association between single nucleotide polymorphism (SNP) variants in IL-5 and symptomatic S. japonicum infection and discuss the potential role of IL-5 in other helminth infections. Fundamental to disease and morbidity control is adequate and effective diagnosis and surveillance of disease. We discuss the role of sICAM-1 and TNFR-I and -II as candidate markers for schistosome-induced hepatomegaly and fibrosis, and their potential for assessing disease stage and progression in schistosomiasis.

Two important recent advances in Leishmania immunology are: (i) the demonstration of a dramatic dichotomy in T helper 1 versus T helper 2 subset expansion leading to protection versus disease exacerbation; and (ii) analysis of the macrophage activation pathways leading to enhanced intracellular killing of parasites, in particular the tumour necrosis factor α (TNFα)-dependent sustained induction of the inducible nitric oxide synthase gene (Nos2) leading to the generation of large amounts of nitric oxide (NO). Given the broad spectrum of disease phenotypes in human leishmaniasis, one might predict that a genetic defect at any key point in this macrophage activation pathway and/or in pathways leading to activation of different T cell subsets, and the latter may be a pleiotropic effect of the former, will contribute to disease susceptibility. By studying disease in genetically-defined inbred mouse strains, it has been possible to identify 5 regions of the murine genome carrying leishmanial susceptibility genes. The genes include: (i) Scl-2 (mouse chromosme 4/human chromosome 9p; candidate Janus tyrosine kinase 1) controlling a unique no lesion growth resistance phenotype to Leishmania mexicana; (ii) Scl-1 (distal mouse chromosome 11/human 17q; candidates Nos2, Sigje, MIP1α, MIP1β) controlling healing versus non-healing responses to L. major; (iii) the ‘T helper 2’ cytokine gene cluster (proximal murine chromosome 11/human 5p; candidates IL4,5,9) controlling later phases of L. major infection; (iv) the major histocompatibility complex (MHC: H-2 in mouse, HLA in man: mouse chromosome 17/human 6p; candidates class II and class III including TNFα/β genes); and (v) Nramp1, the positionally cloned candidate for the murine macrophage resistance gene Ity/Lsh/Bcg (mouse chromosome 1/human 2q35). This review examines these 5 regions and the candidate genes within them, reflecting on their current status as candidates for human disease susceptibility genes.

The current epidemic of human obesity implies that whilst energy balance appears to be regulated, the extent of this regulatory process is being overwhelmed in large numbers of the population by environmental changes. Clearly, the shift towards positive energy balance reflects both alterations in energy intake and decreases in physical activity. Increased energy intake and, in particular, the rising proportion of energy from fat is linked with obesity. However, on a population level reduced levels of activity probably play the predominant role. It is apparent that individual susceptibility to weight gain varies enormously. The factors underlying this susceptibility are an area of intense research interest. Variations in BMR from that predicted appear to be linked to the propensity to gain weight. The genes responsible for this variation may include uncoupling proteins-2 and -3, with a number of studies showing a link with obesity. However, in vivo studies of these proteins have not yet demonstrated a physiological role for them that would explain the link with obesity. Non-exercise activity thermogenesis may also protect from weight gain, but the regulation of this type of thermogenesis is unclear, although the sympathetic nervous system may be important. A profusion of hormones, cytokines and neurotransmitters is involved in regulating energy intake, but whilst mutations in leptin and the melanocortin-3 receptor are responsible for rare monogenic forms of obesity, their wider role in common polygenic obesity is not known. Much current work is directed at examining the interplay between genetic background and environmental factors, in particular diet, that both lead to positive energy balance and seem to make it so hard for many obese subjects to lose weight.

At least six types of gene–environment interactions (GEI) have been proposed (Kouhry and Wagener, 1993) In the first type, neither the environmental exposure (EE) nor the genetic risk factor (GRF) have any effect by themselves, but interaction between them causes disease. This is the case of phenylalanine exposure and the phenylketonuria genotype. Type 2 is a situation in which the GRF has no effect on disease in the absence of exposure, but exacerbates the effects of the latter. This is the most important type of GEI in relation to metabolic susceptibility genes and human carcinogenesis. The third type is the converse of the second (EE is ineffective per se, but enhances the effect of GRF). Type 4 occurs when both EE and GRF increase the risk for disease, but the combination is interactive or synergistic: an example is the interaction between Xeroderma Pigmentosum and UV radiation. Types 5 and 6, according to the classification proposed by Kouhry, refer to cases in which the GRF is protective.

The model of GEI that is emerging as the most important in chemical carcinogenesis refers to metabolic susceptibility genes. The general population can be divided into subgroups depending on their susceptibility to the action of carcinogens, based on their ability to metabolize such compounds to electrophilic, reactive metabolites (which form adducts with DNA), or, respectively, electrophobic metabolites that are excreted. The present contribution is a short review of the relevant literature, with particular emphasis on some polymorphisms involved in dietary exposures. In addition, the practical implications of genetic testing in this field are discussed.

Many studies have shown that overall dietary patterns, dietary components consumed, or mode of food preparation are all possibly relevant in either reducing or increasing the risk of cancer in animals or man. Yet, dietary intervention studies, stemming from laboratory and epidemiological observational studies have often failed to demonstrate the anticipated protection against cancer. One possible explanation for the discrepancy between the results of various observational and experimental chemo-prevention studies is the lack of control for biological diversity of the participants of these studies. It is suggested that future epidemiological studies provide evidence stratified by status of major metabolic polymorphisms pertinent to the study subject, and that future intervention studies take these differences into account in the design and analysis phases.