Ethnic differences in the BMI-%BF relationships between young Japanese and Australian-Caucasian males living in Australia using dual-energy X-ray absorptiometry

The Body Mass Index (BMI) has been used worldwide as an indicator of fatness. However, the universal cut-off points by the World Health Organisation (WHO) classification may not be appropriate for every ethnic group when consider the relationship with their actual total body fatness(%BF). The application of population-specific classifications to assess BMI may be more relevant to public health. Ethnic differences in the BMI%BF relationship between 45 Japanese and 42 Australian-Caucasian males were assessed using whole body dual-energy X-ray absorptiometry (DXA) scan and anthropometry using a standard protocol. Japanese males had significantly (p<0.05) greater %BF at given BMI values than Australian males. When this is taken into account the newly proposed Asia-Pacific BMI classification of BMI 23 as overweight and 25 as obese may better assess the level of obesity that is associated increased health risks for this population. To clarify the current findings, further studies that compare the relationships across other Japanese populations are recommended.

Ethnic differences in body composition and anthropometric characteristics in Australian Caucasian and urban Indigenous children

The objective was to compare ethnic differences in anthropometry, including size, proportions and fat distribution, and body composition in a cohort of seventy Caucasian (forty-four boys, twenty-six girls) and seventy-four urban Indigenous (thirty-six boys, thirty-eight girls) children (aged 9–15 years). Anthropometric measures (stature, body mass, eight skinfolds, thirteen girths, six bone lengths and five bone breadths) and body composition assessment using dual-energy X-ray absorptiometry were conducted. Body composition variables including total body fat percentage and percentage abdominal fat were determined and together with anthropometric indices, including BMI (kg/m2), abdominal:height ratio (AHtR) and sum of skinfolds, ethnic differences were compared for each sex. After adjustment for age, Indigenous girls showed significantly (P < 0·05) greater trunk circumferences and proportion of overweight and obesity than their Caucasian counterparts. In addition, Indigenous children had a significantly greater proportion (P < 0·05) of trunk fat. The best model for total and android fat prediction included sum of skinfolds and age in both sexes (>93 % of variation). Ethnicity was only important in girls where abdominal circumference and AHtR were included and Indigenous girls showed significantly (P < 0·05) smaller total/android fat deposition than Caucasian girls at the given abdominal circumference or AHtR values. Differences in anthropometric and fat distribution patterns in Caucasian and Indigenous children may justify the need for more appropriate screening criteria for obesity in Australian children relevant to ethnic origin.

Ethnic differences in body fat distribution among Asian pre-pubertal children: A cross-sectional multicenter study

Background Ethnic differences in body fat distribution contribute to ethnic differences in cardiovascular morbidities and diabetes. However few data are available on differences in fat distribution in Asian children from various backgrounds. Therefore, the current study aimed to explore ethnic differences in body fat distribution among Asian children from four countries. Methods A total of 758 children aged 8-10 y from China, Lebanon, Malaysia and Thailand were recruited using a non-random purposive sampling approach to enrol children encompassing a wide BMI range. Height, weight, waist circumference (WC), fat mass (FM, derived from total body water [TBW] estimation using the deuterium dilution technique) and skinfold thickness (SFT) at biceps, triceps, subscapular, supraspinale and medial calf were collected. Results After controlling for height and weight, Chinese and Thai children had a significantly higher WC than their Lebanese and Malay counterparts. Chinese and Thais tended to have higher trunk fat deposits than Lebanese and Malays reflected in trunk SFT, trunk/upper extremity ratio or supraspinale/upper extremity ratio after adjustment for age and total body fat. The subscapular/supraspinale skinfold ratio was lower in Chinese and Thais compared with Lebanese and Malays after correcting for trunk SFT. Conclusions Asian pre-pubertal children from different origins vary in body fat distribution. These results indicate the importance of population-specific WC cut-off points or other fat distribution indices to identify the population at risk of obesity-related health problems.

Ethnic differences in lipid metabolism in two groups of obese South African women

There is a higher prevalence of ischemic heart disease (IHD) in South African white than black women. The objective of this study was to determine biochemical explanations for this prevalence. The study group contained 15 obese black women (OBW) and 14 obese white women (OWW), ah premenopausal, who were examined after an overnight fast. Anthropometric measurements and blood concentrations of glucose, non-esterified fatty acids (NEFAs), catecholamines, plasminogen activator inhibitor-1, C-peptide, proinsulin, lipograms, cortisol, growth hormone, and post-heparin Lipoprotein Lipase activity were measured during an oral glucose tolerance test (OGTT), Body composition was measured using bioelectrical impedance analysis, and subcutaneous and visceral fat mass were assessed with CT-scans. Visceral fat area was higher in OWW (139.7 +/- 10.7 cm(2)) than in OBW (72.3 +/- 3.9 cm(2)) (P < 0.01), as were fasting and 3 h triglyceride concentrations (P < 0.05 for all). OWW also had higher NEFA levels than OBW at 3 and 4 h compared, with OBW (P < 0.05 for both). Fasting cortisol (266 +/- 24 vs. 197 +/- 19 nmol/l; P < 0.05) was higher in OWW than in OBW. These data demonstrate that OWW have higher visceral fat mass than OBW, which may lead to a more atherogenic fasting and postprandial Lipid profile. The higher cortisol levels of the OWW may promote visceral fat deposition. - Punyadeera, C., M-T. van der Merwe, N.J. Crowther, M. Toman, C. P. Schlaphoff, and I. P. Gray. Ethnic differences in lipid metabolism in two groups of obese South African women.

Role demands and work-family balance experience in Malaysia : the different moderating effects of collectivism and gender role identity among diverse ethnic groups

The purpose of this thesis is to examine the influence of ethnic cultural values on the relationship of role demands and the work-family balance (WFB) experience. Past studies have found that the demands from work and family roles have a different impact on the work-family experience in people of different ethnicity. Researchers attribute these results to the cultural differences across the groups. However, there has been no empirical support for these assumptions because most past studies did not explicitly measure the cultural dimension in their design. Therefore, although studies have found ethnic differences in work-family experience, as cultural variables were not measured, it cannot be determined whether these differences were due to the differing ethnic groups’ cultural styles. The present thesis is set up to address this limitation in the literature, employing the Malay and Chinese ethnic groups in Malaysia as the study samples. The investigation consisted of pilot interviews and two survey studies. The interviews were carried out to establish the perception of WFB by target participants of a non-western nation. The first survey served to identify whether the Malay and Chinese ethnic groups residing under the same economic and social systems vary in their perceptions of work and family roles. The second survey tests the research model empirically, that is, whether cultural values moderate the relationship between role demands and WFB and if these moderation effects vary across ethnic groups. From the interviews, the results indicated that work-family experience is not a universal experience, but is partly culture-specific. Specifically, in the case of Malaysia, WFB is very much observed from the role obligation perspective. In particular, balance is perceived when work duties and household affairs are both adequately fulfilled. On the other hand, the conceptualisation of WFB in terms of role satisfaction and role interference also emerged in the interviews, suggesting the universality of these constructs across cultures. The findings from Survey One indicated that participants of different ethnicities in this study do not differ greatly in their perceptions regarding their participation in work and family roles. Generally, these participants revealed the less traditional attitudes towards women’s participation in work and family roles. However, variations were observed between the two groups in terms of reasons for working, spouses’ preferences towards their employment, and the extent to which their work role is perceived to impede their normative role performance in the household. Despite these differences, the Malay and Chinese ethnic groups showed more similarities than differences in their perceptions of work and family. The findings from Survey Two, which tested the research model, produced mixed results. On the whole, the results showed that the cultural dimensions examined in this study (i.e. collectivism, work identity and family identity) did influence the relationship between role demands and WFB experience, thus providing empirical evidence for the assumption in the literature that the relationship between role demand and work-family experience is moderated by cultural values. Most importantly, support was found for the proposition that these moderation effects vary between the Malay and Chinese ethnic groups. Moreover, this study also found evidence that Malays and Chinese differ significantly on collectivism and work identity cultural dimensions where Malays are found to be more collectivist than the Chinese, while work identity is stronger in the Chinese than in the Malays. There is no difference in the levels of family identity between the two groups. Of all the three moderators, work identity was deemed the most important because many of the supported hypotheses pertained to the work identity moderating effects. In contrast, family identity does not seem to have much moderating influence on role demand-WFB relationships, while the results for the collectivism moderator are mixed. As such, although not conclusive, it can be deduced that variations in the effects of role demand on work-family experience across ethnicity are a result of the groups’ cultural differences, thereby supporting the assumption in the literature.

Weight-related differences in glucose metabolism and free fatty acid production in two South African population groups

OBJECTIVE The effects of free fatty acids (FFA), leptin, tumour necrosis factor (TNF) alpha and body fat distribution on in vivo oxidation of a glucose load were studied in two South African ethnic groups. DESIGN AND MEASUREMENTS Anthropometric and various metabolic indices were measured at fasting and during a 7h oral glucose tolerance test (OGTT). Body composition was measured using bioelectrical impedance analysis and subcutaneous and visceral fat mass was assessed using a five- and two-level CT-scan respectively. Glucose oxidation was evaluated by measuring the ratio of (13)CO(2) to (12)CO(2) in breath following ingestion of 1-(13)C-labelled glucose. SUBJECTS Ten lean black women (LBW), ten obese black women (OBW), nine lean white women (LWW) and nine obese white women (OWW) were investigated after an overnight fast. RESULTS Visceral fat levels were significantly higher (P < 0.01) in obese white than black women, despite similar body mass indexes (BMIs). There were no ethnic differences in glucose oxidation however; in the lean subjects of both ethnic groups the area under the curve (AUC) was higher than in obese subjects (P < 0.05 for both) and was found to correlate negatively with weight (r = -0.69, P < 0.01) after correcting for age. Basal TNF alpha concentrations were similar in all groups. Percentage suppression of FFAs at 30 min of the OCTT was 24 +/- 12% in OWW and - 38 +/- 23% (P < 0.05) in OBW, ie the 30 min FFA level was higher than the fasting level in the latter group. AUC for FFAs during the late postprandial period (120 - 420 min) was significantly higher in OWW than OBW (P < 0.01) and LWW (P < 0.01) and correlated positively with visceral fat mass independent of age (r = 0.78, P < 0.05) in the OWW only. Leptin levels were higher (P < 0.01) both at fasting and during the course of the OCTT in obese women from both ethnic groups compared to the lean women. CONCLUSIONS Glucose oxidation is reduced in obese subjects of both ethnic groups; inter- and intra-ethnic differences were observed in visceral fat mass and FFA production and it is possible that such differences may play a role in the differing prevalences of obesity-related disorders that have been reported in these two populations.

Assessment of body composition of Sri Lankan Australian children using ethnic specific equations

Since ethnic differences exist in body composition, assessment methods need to be validated prior to use in different populations. This study attempts to validate the use of Sri Lankan based body composition assessment tools on a group of 5 - 15 year old Australian children of Sri Lankan origin. The study was conducted at the Body Composition Laboratory of the Children’s Nutrition Research Centre at the Royal Children’s Hospital, Brisbane, Australia. Height (Ht), weight (Wt), segmental length (Lsegment name) and skinfold thickness (SFT) were measured. The whole body and segmental bio impedance analysis (BIA) were also measured. The body composition determined by the deuterium dilution technique (criterion method) was compared with the assessments done using prediction equations developed on Sri Lankan children. 27 boys and 15 girls were studied. All predictions of body composition parameters, except percentage fat mass (FM) assessed by the SFT-FM equation in girls gave statistically significant correlations with the criterion method. They had a low mean bias and most were not influenced by the measured parameter. Although living in a different socioeconomic state, the equations developed on children of the same ethnic background gives a better predictive value of body composition. This highlights the ethnic influence on body composition.

Associations among body size dissatisfaction, perceived dietary control, and diet history in African American and European American women

European American (EA) women report greater body dissatisfaction and less dietary control than do African American (AA) women. This study investigated whether ethnic differences in dieting history contributed to differences in body dissatisfaction and dietary control, or to differential changes that may occur during weight loss and regain. Eighty-nine EA and AA women underwent dual-energy X-ray absorptiometry to measure body composition and completed questionnaires to assess body dissatisfaction and dietary control before, after, and one year following, a controlled weight-loss intervention. While EA women reported a more extensive dieting history than AA women, this difference did not contribute to ethnic differences in body dissatisfaction and perceived dietary control. During weight loss, body satisfaction improved more for AA women, and during weight regain, dietary self-efficacy worsened to a greater degree for EA women. Ethnic differences in dieting history did not contribute significantly to these differential changes. Although ethnic differences in body image and dietary control are evident prior to weight loss, and some change differentially by ethnic group during weight loss and regain, differences in dieting history do not contribute significantly to ethnic differences in body image and dietary control.

Body composition and its relationship to metabolic risk factors in Asian children

Obesity is a major public health problem in both developed and developing countries. The body mass index (BMI) is the most common index used to define obesity. The universal application of the same BMI classification across different ethnic groups is being challenged due to the inability of the index to differentiate fat mass (FM) and fat�]free mass (FFM) and the recognized ethnic differences in body composition. A better understanding of the body composition of Asian children from different backgrounds would help to better understand the obesity�]related health risks of people in this region. Moreover, the limitations of the BMI underscore the necessity to use where possible, more accurate measures of body fat assessment in research and clinical settings in addition to BMI, particularly in relation to the monitoring of prevention and treatment efforts. The aim of the first study was to determine the ethnic difference in the relationship between BMI and percent body fat (%BF) in pre�]pubertal Asian children from China, Lebanon, Malaysia, the Philippines, and Thailand. A total of 1039 children aged 8�]10 y were recruited using a non�]random purposive sampling approach aiming to encompass a wide BMI range from the five countries. Percent body fat (%BF) was determined using the deuterium dilution technique to quantify total body water (TBW) and subsequently derive proportions of FM and FFM. The study highlighted the sex and ethnic differences between BMI and %BF in Asian children from different countries. Girls had approximately 4.0% higher %BF compared with boys at a given BMI. Filipino boys tended to have a lower %BF than their Chinese, Lebanese, Malay and Thai counterparts at the same age and BMI level (corrected mean %BF was 25.7�}0.8%, 27.4�}0.4%, 27.1�}0.6%, 27.7�}0.5%, 28.1�}0.5% for Filipino, Chinese, Lebanese, Malay and Thai boys, respectively), although they differed significantly from Thai and Malay boys. Thai girls had approximately 2.0% higher %BF values than Chinese, Lebanese, Filipino and Malay counterparts (however no significant difference was seen among the four ethnic groups) at a given BMI (corrected mean %BF was 31.1�}0.5%, 28.6�}0.4%, 29.2�}0.6%, 29.5�}0.6%, 29.5�}0.5% for Thai, Chinese, Lebanese, Malay and Filipino girls, respectively). However, the ethnic difference in BMI�]%BF relationship varied by BMI. Compared with Caucasians, Asian children had a BMI 3�]6 units lower for a given %BF. More than one third of obese Asian children in the study were not identified using the WHO classification and more than half were not identified using the International Obesity Task Force (IOTF) classification. However, use of the Chinese classification increased the sensitivity by 19.7%, 18.1%, 2.3%, 2.3%, and 11.3% for Chinese, Lebanese, Malay, Filipino and Thai girls, respectively. A further aim of the first study was to determine the ethnic difference in body fat distribution in pre�]pubertal Asian children from China, Lebanon, Malaysia, and Thailand. The skin fold thicknesses, height, weight, waist circumference (WC) and total adiposity (as determined by deuterium dilution technique) of 922 children from the four countries was assessed. Chinese boys and girls had a similar trunk�]to�]extremity skin fold thickness ratio to Thai counterparts and both groups had higher ratios than the Malays and Lebanese at a given total FM. At a given BMI, both Chinese and Thai boys and girls had a higher WC than Malays and Lebanese (corrected mean WC was 68.1�}0.2 cm, 67.8�}0.3 cm, 65.8�}0.4 cm, 64.1�}0.3 cm for Chinese, Thai, Lebanese and Malay boys, respectively; 64.2�}0.2 cm, 65.0�}0.3 cm, 62.9�}0.4 cm, 60.6�}0.3 cm for Chinese, Thai, Lebanese and Malay girls, respectively). Chinese boys and girls had lower trunk fat adjusted subscapular/suprailiac skinfold ratio compared with Lebanese and Malay counterparts. The second study aimed to develop and cross�]validate bioelectrical impedance analysis (BIA) prediction equations of TBW and FFM for Asian pre�]pubertal children from China, Lebanon, Malaysia, the Philippines, and Thailand. Data on height, weight, age, gender, resistance and reactance measured by BIA were collected from 948 Asian children (492 boys and 456 girls) aged 8�]10 y from the five countries. The deuterium dilution technique was used as the criterion method for the estimation of TBW and FFM. The BIA equations were developed from the validation group (630 children randomly selected from the total sample) using stepwise multiple regression analysis and cross�]validated in a separate group (318 children) using the Bland�]Altman approach. Age, gender and ethnicity influenced the relationship between the resistance index (RI = height2/resistance), TBW and FFM. The BIA prediction equation for the estimation of TBW was: TBW (kg) = 0.231�~Height2 (cm)/resistance (ƒ¶) + 0.066�~Height (cm) + 0.188�~Weight (kg) + 0.128�~Age (yr) + 0.500�~Sex (male=1, female=0) . 0.316�~Ethnicity (Thai ethnicity=1, others=0) �] 4.574, and for the estimation of FFM: FFM (kg) = 0.299�~Height2 (cm)/resistance (ƒ¶) + 0.086�~Height (cm) + 0.245�~Weight (kg) + 0.260�~Age (yr) + 0.901�~Sex (male=1, female=0) �] 0.415�~Ethnicity (Thai ethnicity=1, others=0) �] 6.952. The R2 was 88.0% (root mean square error, RSME = 1.3 kg), 88.3% (RSME = 1.7 kg) for TBW and FFM equation, respectively. No significant difference between measured and predicted TBW and between measured and predicted FFM for the whole cross�]validation sample was found (bias = �]0.1�}1.4 kg, pure error = 1.4�}2.0 kg for TBW and bias = �]0.2�}1.9 kg, pure error = 1.8�}2.6 kg for FFM). However, the prediction equation for estimation of TBW/FFM tended to overestimate TBW/FFM at lower levels while underestimate at higher levels of TBW/FFM. Accuracy of the general equation for TBW and FFM compared favorably with both BMI�]specific and ethnic�]specific equations. There were significant differences between predicted TBW and FFM from external BIA equations derived from Caucasian populations and measured values in Asian children. There were three specific aims of the third study. The first was to explore the relationship between obesity and metabolic syndrome and abnormalities in Chinese children. A total of 608 boys and 800 girls aged 6�]12 y were recruited from four cities in China. Three definitions of pediatric metabolic syndrome and abnormalities were used, including the International Diabetes Federation (IDF) and National Cholesterol Education Program (NCEP) definition for adults modified by Cook et al. and de Ferranti et al. The prevalence of metabolic syndrome varied with different definitions, was highest using the de Ferranti definition (5.4%, 24.6% and 42.0%, respectively for normal�]weight, overweight and obese children), followed by the Cook definition (1.5%, 8.1%, and 25.1%, respectively), and the IDF definition (0.5%, 1.8% and 8.3%, respectively). Overweight and obese children had a higher risk of developing the metabolic syndrome compared to normal�]weight children (odds ratio varied with different definitions from 3.958 to 6.866 for overweight children, and 12.640�]26.007 for obese children). Overweight and obesity also increased the risk of developing metabolic abnormalities. Central obesity and high triglycerides (TG) were the most common while hyperglycemia was the least frequent in Chinese children regardless of different definitions. The second purpose was to determine the best obesity index for the prediction of cardiovascular (CV) risk factor clustering across a 2�]y follow�]up among BMI, %BF, WC and waist�]to�]height ratio (WHtR) in Chinese children. Height, weight, WC, %BF as determined by BIA, blood pressure, TG, high�]density lipoprotein cholesterol (HDL�]C), and fasting glucose were collected at baseline and 2 years later in 292 boys and 277 girls aged 8�]10 y. The results showed the percentage of children who remained overweight/obese defined on the basis of BMI, WC, WHtR and %BF was 89.7%, 93.5%, 84.5%, and 80.4%, respectively after 2 years. Obesity indices at baseline significantly correlated with TG, HDL�]C, and blood pressure at both baseline and 2 years later with a similar strength of correlations. BMI at baseline explained the greatest variance of later blood pressure. WC at baseline explained the greatest variance of later HDL�]C and glucose, while WHtR at baseline was the main predictor of later TG. Receiver�]operating characteristic (ROC) analysis explored the ability of the four indices to identify the later presence of CV risk. The overweight/obese children defined on the basis of BMI, WC, WHtR or %BF were more likely to develop CV risk 2 years later with relative risk (RR) scores of 3.670, 3.762, 2.767, and 2.804, respectively. The final purpose of the third study was to develop age�] and gender�]specific percentiles of WC and WHtR and cut�]off points of WC and WHtR for the prediction of CV risk in Chinese children. Smoothed percentile curves of WC and WHtR were produced in 2830 boys and 2699 girls aged 6�]12 y randomly selected from southern and northern China using the LMS method. The optimal age�] and gender�]specific thresholds of WC and WHtR for the prediction of cardiovascular risk factors clustering were derived in a sub�]sample (n=1845) by ROC analysis. Age�] and gender�]specific WC and WHtR percentiles were constructed. The WC thresholds were at the 90th and 84th percentiles for Chinese boys and girls, respectively, with sensitivity and specificity ranging from 67.2% to 83.3%. The WHtR thresholds were at the 91st and 94th percentiles for Chinese boys and girls, respectively, with sensitivity and specificity ranging from 78.6% to 88.9%. The cut�]offs of both WC and WHtR were age�] and gender�]dependent. In conclusion, the current thesis quantifies the ethnic differences in the BMI�]%BF relationship and body fat distribution between Asian children from different origins and confirms the necessity to consider ethnic differences in body composition when developing BMI and other obesity index criteria for obesity in Asian children. Moreover, ethnicity is also important in BIA prediction equations. In addition, WC and WHtR percentiles and thresholds for the prediction of CV risk in Chinese children differ from other populations. Although there was no advantage of WC or WHtR over BMI or %BF in the prediction of CV risk, obese children had a higher risk of developing the metabolic syndrome and abnormalities than normal�]weight children regardless of the obesity index used.

Prevalence and predictors of refractive error in a genetically isolated population : the Norfolk Island Eye Study

BACKGROUND: We aimed to determine the prevalence and associations of refractive error on Norfolk Island. DESIGN: Population-based study on Norfolk Island, South Pacific. PARTICIPANTS: All permanent residents on Norfolk Island aged ≥ 15 years were invited to participate. METHODS: Patients underwent non-cycloplegic autorefraction, slit-lamp biomicroscope examination and biometry assessment. Only phakic eyes were analysed. MAIN OUTCOME MEASURES: Prevalence and multivariate associations of refractive error and myopia. RESULTS: There were 677 people (645 right phakic eyes, 648 left phakic eyes) aged ≥ 15 years were included in this study. Mean age of participants was 51.1 (standard deviation 15.7; range 15-81). Three hundred and seventy-six people (55.5%) were female. Adjusted to the 2006 Norfolk Island population, prevalence estimates of refractive error were as follows: myopia (mean spherical equivalent ≥ -1.0 D) 10.1%, hypermetropia (mean spherical equivalent ≥ 1.0 D) 36.6%, and astigmatism 17.7%. Significant independent predictors of myopia in the multivariate model were lower age (P < 0.001), longer axial length (P < 0.001), shallower anterior chamber depth (P = 0.031) and increased corneal curvature (P < 0.001). Significant independent predictors of refractive error were increasing age (P < 0.001), male gender (P = 0.009), Pitcairn ancestry (P = 0.041), cataract (P < 0.001), longer axial length (P < 0.001) and decreased corneal curvature (P < 0.001). CONCLUSIONS: The prevalence of myopia on Norfolk Island is lower than on mainland Australia, and the Norfolk Island population demonstrates ethnic differences in the prevalence estimates. Given the significant associations between refractive error and several ocular biometry characteristics, Norfolk Island may be a useful population in which to find the genetic basis of refractive error.

Common PPARγ variants C161T and Pro12Ala are not associated with inflammatory bowel disease in an Australian cohort

Background & Aims: Peroxisome proliferator-activated receptor (PPAR) γ is a transcription factor, highly expressed in colonic epithelial cells, adipose tissue and macrophages, with an important role in the regulation of inflammatory pathways. The common PPARγ variants C161T and Pro12Ala have recently been associated with Ulcerative Colitis (UC) and an extensive UC phenotype respectively, in a Chinese population. PPARγ Pro12Ala variant homozygotes appear to be protected from the development of Crohn's disease (CD) in European Caucasians. Methods: A case-control study was performed for both variants (CD n=575, UC n=306, Controls n=360) using a polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis in an Australian IBD cohort. A transmission disequilibrium test was also performed using CD trios for the PPARγ C161T variant. Genotype-phenotype analyses were also undertaken. Results: There was no significant difference in genotype distribution data or allele frequency between CD and UC patients and controls. There was no difference in allele transmission for the C161T variant. No significant relationship between the variants and disease location was observed. Conclusions: We were unable to replicate in a Caucasian cohort the recent association between PPARγ C161T and UC or between PPARγ Pro12Ala and an extensive UC phenotype in a Chinese population. There are significant ethnic differences in genetic susceptibility to IBD and its phenotypic expression.

The cytochrome P-450 isoenzyme CYP2E1 in the biological processing of industrial chemicals : consequences for occupational and environmental medicine

The importance of the isoform CYP2E1 of the human cytochrome P-450 superfamily of enzymes for occupational and environmental medicine is derived from its unique substrate spectrum that includes a number of highly important high-production chemicals, such as aliphatic and aromatic hydrocarbons, solvents and industrial monomers (i.a. alkanes, alkenes, aromatic and halogenated hydrocarbons). Many polymorphic genes, such as CYP2E1, show considerable differences in allelic distribution between different human populations. The polymorphic nature of the human CYP2E1 gene is significant for inter-individual differences in toxicity of its substrates. Since the substrate spectrum of CYP2E1 includes many compounds of basic relevance to industrial toxicology, a rationale for metabolic interactions of different CYP2E1 substrates is provided. In-depth research into the inter-individual phenotypic differences of human CYP2E1 enzyme activities was enabled by the recognition that the 6-hydroxylation of the drug chlorzoxazone is mediated by CYP2E1. Studies on CYP2E1 phenotyping have pointed to inter-individual variations in enzyme activities. There are consistent ethnic differences in CYP2E1 enzyme expression, mostly demonstrated between European and Japanese populations, which point to a major impact of genetic factors. The most frequently studied genetic polymorphisms are the restriction fragment length polymorphisms PstI/RsaI (mutant allele: CYP2E1*5B) located in the 5′-flanking region of the gene, as well as the DraI polymorphism (mutant allele: CYP2E1*6) located in intron 6. These polymorphisms are partly related, as they form the common allele designated CYP2E1*5A. Striking inter-ethnic differences between Europeans and Asians appear with respect to the frequencies of the CYP2E1*5A allele (only approximately 5% of Europeans are heterozygous, but 37% of Asians are, whilst 6% of Asians are homozygous). Available studies indicate a wide variation in human CYP2E1 expression, which are very likely based on complex gene-environment interactions. Major inter-ethnic differences are apparent on the genotyping and the phenotyping levels. Selected cases are presented where inter-ethnic variations of CYP2E1 may provide likely explanations for unexplained findings concerning industrial chemicals that are CYP2E1 substrates. Possible consequences of differential inter-individual and inter-ethnic susceptibilities are related to individual expressions of clinical symptoms of chemical toxicity, to results of biological monitoring of exposed workers, and to the interpretation of results of epidemiological or molecular-epidemiological studies.

Relevance of the deletion polymorphisms of the glutathione S-transferases GSTT1 and GSTM1 in pharmacology and toxicology

Although cytosolic glutathione S-transferase (GST) enzymes occupy a key position in biological detoxification processes, two of the most relevant human isoenzymes, GSTT1-1 and GSTM1-1, are genetically deleted (non-functional alleles GSTT1*0 and GSTM1*0) in a high percentage of the human population, with major ethnic differences. The structures of the GSTT and GSTM gene areas explain the underlying genetic processes. GSTT1-1 is highly conserved during evolution and plays a major role in phase-II biotransformation of a number of drugs and industrial chemicals, e.g. cytostatic drugs, hydrocarbons and halogenated hydrocarbons. GSTM1-1 is particularly relevant in the deactivation of carcinogenic intermediates of polycyclic aromatic hydrocarbons. Several lines of evidence suggest that hGSTT1-1 and/or hGSTM1-1 play a role in the deactivation of reactive oxygen species that are likely to be involved in cellular processes of inflammation, ageing and degenerative diseases. There is cumulating evidence that combinations of the GSTM1*0 state with other genetic traits affecting the metabolism of carcinogens (CYP1A1, GSTP1) may predispose the aero-digestive tract and lung, especially in smokers, to a higher risk of cancer. The GSTM1*0 status appears also associated with a modest increase in the risk of bladder cancer, consistent with a GSTM1 interaction with carcinogenic tobacco smoke constituents. Both human GST deletions, although largely counterbalanced by overlapping substrate affinities within the GST superfamily, have consequences when the organism comes into contact with distinct man-made chemicals. This appears relevant in industrial toxicology and in drug metabolism.

Metabolic response to a mixed meal in obese and lean women from two South African populations

Objective Lower lipid and insulin levels are found during a glucose-tolerance test in obese black than obese white South African women. Therefore, β-cell function and lipid metabolism were compared in these populations during a mixed meal. Research Methods and Procedures Blood concentrations of glucose, free fatty acids (FFAs), insulin, lipograms, and in vivo FFA oxidation were determined at fasting and for 7 hours after oral administration of a mixed emulsion containing glucose-casein-sucrose-lipid and [1-13C] palmitic acid in 8 lean black women (LBW), 10 obese black women (OBW), 9 lean white women (LWW), and 10 obese white women (OWW). Subcutaneous and visceral fat mass was assessed by computerized tomography. Results Visceral fat area was higher in OWW (152.7 ± 17.0 cm2) than OBW (80.0 ± 6.7 cm2; p < 0.01). In OBW, 30-minute insulin levels were higher (604.3 ± 117.6 pM) than OWW (311.0 ± 42.9 pM; p < 0.05). Total triglyceride was higher in OWW (706.7 ± 96.0 mM × 7 hours) than OBW (465.7 ± 48.2 mM × 7 hours; p < 0.05) and correlated with visceral fat area (β = 0.38, p = 0.05). Palmitate oxidation was higher in lean than obese women in both ethnic groups and correlated negatively with fat mass (β = −0.58, p < 0.005). Discussion The higher 30-minute insulin response in OBW may reflect a higher insulinotropic effect of FFAs or glucose. The elevated triglyceride level of OWW may be due to their higher visceral fat mass and possibly reduced clearance by adipose tissue.