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Africa is home to genetically diverse human populations. We compared the genetic structure of the Wolaita ethnic population from Southern Ethiopia (WETH, n=120) with HapMap populations using genome-wide variants. We investigated allele frequencies of 443 clinically and pharmacogenomically relevant genetic variants in WETH compared with HapMap populations. We found that WETH were genetically most similar to the Kenya Maasai and least similar to the Japanese in HapMap. Variant alleles associated with increased risk of adverse reactions to drugs used for treating tuberculosis (rs1799929 and rs1495741 in NAT2), thromboembolism (rs7294, rs9923231 and rs9934438 in VKORC1), and HIV/AIDS and solid tumors (rs2242046 in SLC28A1) had significantly higher frequencies in WETH compared with African ancestry HapMap populations. Our results illustrate that clinically relevant pharmacogenomic loci display allele frequency differences among African populations. We conclude that drug dosage guidelines for important global health diseases should be validated in genetically diverse African populations. [ABSTRACT FROM AUTHOR]

Semicarbazide-sensitive amine oxidase (SSAO) also functions as a vascular-adhesion protein (VAP-1). The nature of the target site on lymphocytes to which endothelial-cell SSAO/VAP-1 binds is unknown. We have shown that amino sugars (galactosamine, glucosamine and mannosamine), which are not SSAO substrates, can bind to the enzyme as reversible inhibitors. Thus, they serve as a model system in which to study the interaction process. Binding occurred during substrate (benzylamine) oxidation but not when the amino sugar was incubated, for extended periods, with SSAO alone. These results suggest that one, or more of the products of the SSAO-catalysed amine oxidation might be necessary for the inhibitory process to occur. Two of the reaction products of benzylamine oxidation, benzaldehyde and ammonia were found to have no effect on the inhibition of SSAO by galactosamine. Preincubation of the enzyme with galactosamine plus H2O2 was, however, found to result in time-dependent inhibition. This is not a result of the non-enzymic reaction between H2O2 and the amino sugar, since preincubation of galactosamine with H2O2 alone, for extended periods, did not give rise to an inhibitory species. The amount of exogenously added H2O2 necessary for inhibition was very much greater than that formed during substrate oxidation. These results suggest that the H2O2 formed as a product of the SSAO-catalysed oxidation reaction is more efective in promoting the binding of amino sugars. [ABSTRACT FROM AUTHOR]

Amine oxidase substrates such as benzylamine and methylamine have been shown to stimulate glucose uptake by increasing the recruitment of the glucose transporter GLUT4 from vesicles within the cell to the cell surface. Inhibition of this effect by the presence of semicarbazide and catalase led to the suggestion that the process is mediated by the H2O2 produced in the oxidation of these amines. Tyramine, which is a substrate for both MAO and SSAO, can also stimulate this process and in that case both MAO and SSAO inhibitors attenuate the effect. Benzylamine does not occur physiologically and tyramine is normally present in only very low amounts. We have suggested that adrenaline, which also stimulates glucose metabolism through adrenoceptors, may act as the physiological substrate for GLUT4 recruitment. It is a substrate for MAO but not SSAO. However, oxidation of adrenaline by MAO releases both H2O2 and methylamine for further oxidation by SSAO. In order to gain a fuller understanding of this process we have performed simulation studies that may be used to assess the contributions of the amine oxidases to the process under a variety of conditions. The results are consistent with the experimentally observed behaviour. This approach not only helps to establish the feasibility of this process but also allows behaviour prediction and the identification of further experimental approaches. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To compare body mass index (BMI) in four diet groups (meat-eaters, fish-eaters, vegetarians and vegans) in the Oxford cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Oxford) and to investigate lifestyle and dietary factors associated with any observed differences. DESIGN: Cross-sectional analysis of self-reported dietary, anthropometric and lifestyle data. PARTICIPANTS: A total of 37 875 healthy men and women aged 20-97 y participating in EPIC-Oxford. RESULTS: Age-adjusted mean BMI was significantly different between the four diet groups, being highest in the meat-eaters (24.41 kg/m[SUP2] in men, 23.52 kg/m[SUP2] in women) and lowest in the vegans (22.49 kg/m[SUP2] in men, 21.98 kg/m[SUP2] in women). Fish-eaters and vegetarians had similar, intermediate mean BMI. Differences in lifestyle factors including smoking, physical activity and education level accounted for less than 5% of the difference in mean age-adjusted BMI between meat-eaters and vegans, whereas differences in macronutrient intake accounted for about half of the difference. High protein (as percent energy) and low fibre intakes were the dietary factors most strongly and consistently associated with increasing BMI both between and within the diet groups. CONCLUSIONS: Fish-eaters, vegetarians and especially vegans had lower BMI than meat-eaters. Differences in macronutrient intakes accounted for about half the difference in mean BMI between vegans and meat-eaters. High protein and low fibre intakes were the factors most strongly associated with increasing BMI. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationships between plasma concentrations of sex hormones and risk factors for breast cancer.Methods: We investigated the relationship of plasma concentrations of estradiol, progesterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and sex hormone-binding globulin (SHBG) with breast cancer risk factors in 636 premenopausal and 456 postmenopausal women. Risk factor data were obtained from questionnaires and hormone concentrations measured by immunoassays; variations in geometric means were compared using analysis of covariance.Results: SHBG decreased with increasing body mass index and increasing waist-hip ratio both in pre- and postmenopausal women. In postmenopausal women only, estradiol increased with increasing body mass index. In premenopausal women, estradiol decreased with increasing physical activity, estradiol was higher in current than in ex- and non-smokers, and FSH decreased with increasing alcohol intake. No associations were observed between sex hormones and age at menarche, parity, age at menopause, and previous use of oral contraceptives in either pre- or postmenopausal women.Conclusions: Certain factors such as obesity and perhaps waist-hip ratio, physical activity and alcohol consumption, but probably not age at menarche and parity, may mediate their effects on breast cancer risk by changing circulating concentrations of sex hormones. [ABSTRACT FROM AUTHOR]

There are two main histological groups of testicular germ cell tumours, which may have different risk factors. Some authors have analysed potential risk factors by histological group but few consistent differences have been identified. In this paper we examine risk factors for pure seminoma and other tumours using data from the United Kingdom case control study of testicular cancer. Seven hundred and ninety-four cases were included in the study, each with a matched control; 400 cases had pure seminoma tumours, and 394 had other testicular tumours. The risk of seminoma associated with undescended testis was slightly higher than that for other tumours (odds ratio of 5.3 compared with 3.0). When split at the median age at diagnosis, this difference was greater in men aged 32 and over (odds ratio of 11.9 compared with 5.1) than in the younger men (3.0 compared with 2.5). Risks associated with testicular or groin injuries were higher in the non-seminoma group, as was the risk for a history of sexually transmitted disease. The protective effect of a late puberty was more marked for tumours of other histologies. Some differences were also detected for participation in sports. Whilst some of the differences detected may have arisen by chance, the stronger association between undescended testis and pure seminoma has been identified by a number of other studies and may reflect a genuine difference in aetiology. [ABSTRACT FROM AUTHOR]

Endogenous oestradiol is strongly associated with breast cancer risk but its determinants are poorly understood. To test the hypothesis that vegetarians have lower plasma oestradiol and higher sex hormone-binding globulin (SHBG) than meat-eaters we assayed samples from 640 premenopausal women (153 meat-eaters, 382 vegetarians, 105 vegans) and 457 post-menopausal women (223 meat-eaters, 196 vegetarians, 38 vegans). Vegetarians and vegans had lower mean body mass indices (BMI) and lower plasma cholesterol concentrations than meat-eaters, but there were no statistically significant differences between meat-eaters, vegetarians and vegans in pre-or post-menopausal plasma concentrations of oestradiol or SHBG. Before adjusting for BMI there were small differences in the direction expected, with the vegetarians and vegans having higher SHBG and lower oestradiol (more noticeable amongst post-menopausal women) than the meat-eaters. These small differences were essentially eliminated by adjusting for BMI. Thus this study implies that the relatively low BMI of vegetarians and vegans does cause small changes in SHBG and in post-menopausal oestradiol, but that the composition of vegetarian diets may not have any additional effects on these hormones. [ABSTRACT FROM AUTHOR]

Mean serum insulin-like growth factor-I was 9% lower in 233 vegan men than in 226 meat-eaters and 237 vegetarians (P = 0.002). Vegans had higher testosterone levels than vegetarians and meat-eaters, but this was offset by higher sex hormone binding globulin, and there were no differences between diet groups in free testosterone, androstanediol glucuronide or luteinizing hormone. [ABSTRACT FROM AUTHOR]