Ethnic disparities in risk of cardiovascular disease, end-stage renal disease and all-cause mortality: a prospective study among Asian people with Type 2 diabetes.

AIM: To study prospectively the ethnic-specific risks of cardiovascular disease, end-stage renal disease and all-cause mortality in patients with Type 2 diabetes mellitus among native Asian subpopulations. METHODS: A total of 2337 subjects with Type 2 diabetes (70% Chinese, 17% Malay and 13% Asian Indian) were followed for a median of 4.0 years. Time-to-event analysis was used to study the association of ethnicity with adverse outcomes. RESULTS: Age- and gender-adjusted hazard ratios for cardiovascular disease in ethnic Malay and Asian Indian subjects were 2.01 (1.40-2.88; P<0.0001) and 1.60 (1.07-2.41; P=0.022) as compared with Chinese subjects. Adjustment for conventional cardiovascular disease risk factors, including HbA1c , blood pressure and lipid profile, slightly attenuated the hazards in Malay (1.82, 1.23-2.71; P=0.003) and Asian Indian subjects (1.47, 0.95-2.30; P=0.086); However, further adjustment for baseline renal function (estimated GFR) and albuminuria weakened the cardiovascular disease risks in Malay (1.48, 0.98-2.26; P=0.065) but strengthened that in Asian Indian subjects (1.81, 1.14-2.87; P=0.012). Competing-risk regression showed that the age- and gender-adjusted sub-distribution hazard ratio for end-stage renal disease was 1.87 (1.27-2.73; P=0.001) in Malay and 0.39 (0.18-0.83; P=0.015) in Asian Indian subjects. Notably, the difference in end-stage renal disease risk among the three ethnic groups was abolished after further adjustment for baseline estimated GFR and albuminuria. There was no significant difference in risk of all-cause mortality among the three ethnic groups. CONCLUSIONS: Risks of cardiovascular and end-stage renal diseases in native Asian subjects with Type 2 diabetes vary substantially among different ethnic groups. Differences in prevalence of diabetic kidney disease may partially explain the ethnic disparities.

Health-related quality of life of Asian patients with end-stage renal disease (ESRD) in Singapore.

BACKGROUND: This study aimed to identify factors associated with the health-related quality of life (HRQOL) of multiethnic Asian end-stage renal disease (ESRD) patients treated with dialysis. The role of dialysis modality was also explored. METHODS: Data used in this study were from two cross-sectional surveys of Singaporean ESRD patients on haemodialysis (HD) or peritoneal dialysis (PD). In both surveys, participants were assessed using the kidney disease quality of life (KDQOL) instrument and questions assessing socio-demographic characteristics. Clinical data including co-morbidity (measured by Charlson comorbidity index [CCI]), albumin level, haemoglobin level, and dialysis-related variables (e.g. dialysis vintage and dialysis adequacy) were retrieved from medical records. The 36-item KDQOL (KDQOL-36) was used to generate three summary scores (physical component summary [PCS], mental component summary [MCS] and kidney disease component summary [KDCS]) and two health utility scores (Short Form 6-dimension [SF-6D] and EuroQol 5-dimension [EQ-5D]). Linear regression analysis was performed to examine the association of factors with each of the HRQOL scale scores. RESULTS: Five hundred and two patients were included in the study (mean age 57.1 years; male 52.4 %; HD 236, PD 266). Mean [standard deviation (SD)] PCS, MCS and KDCS scores were 37.9 (9.7), 46.4 (10.8) and 57.6 (18.1), respectively. Mean (SD) health utility score was 0.66 (0.12) for SF-6D and 0.60 (0.21) for EQ-5D. In multivariate regression analysis, factors found to be significantly associated with better HRQOL included: young (<45 years) or old age (>60 years), low CCI (<5), high albumin (≥37 g/l) and high haemoglobin (≥11 g/dl) with PCS; long dialysis vintage (≥3.5 years) with MCS; old age, Malay ethnicity and PD modality with KDCS; low CCI, high albumin and high haemoglobin with EQ-5D and high albumin with SF-6D. CONCLUSIONS: Clinical characteristics are better predictors of HRQOL in ESRD patients than socio-demographics in Singapore. Dialysis modality has no impact on the health utility of those patients.

Pharmacogenomic diversity in Singaporean populations and Europeans.

Differences in the frequency of pharmacogenomic variants may influence inter-population variability in drug efficacy and risk of adverse drug reactions (ADRs). We investigated the diversity of ∼ 4500 genetic variants in key drug-biotransformation and -response genes among three South East Asian populations compared with individuals of European ancestry. We compared rates of reported ADRs in these Asian populations to determine if the allelic differentiation corresponded to an excess of the associated ADR. We identified an excess of ADRs related to clopidogrel in Singaporean Chinese, consistent with a higher frequency of a known risk variant in CYP2C19 in that population. We also observed an excess of ADRs related to platinum compounds in Singaporean CHS, despite a very low frequency of known ADR risk variants, suggesting the presence of additional genetic and non-genetic risk factors. Our results point to substantial diversity at specific pharmacogenomic loci that may contribute to inter-population variability in drug response phenotypes.

Long-term exposure to particulate matter and all-cause and cause-specific mortality in an analysis of multiple Asian cohorts.

BACKGROUND: Exposure to ambient air pollution is associated with a significant number of deaths. Much of the evidence associating air pollution with adverse effects is from North American and Europe, partially due to incomplete data in other regions limiting location specific examinations. The aim of the current paper is to leverage satellite derived air quality data to examine the relationship between ambient particulate matter and all-cause and cause-specific mortality in Asia. METHODS: Six cohorts from the Asia Cohort Consortium provided residential information for participants, recruited between 1991 and 2008, across six countries (Bangladesh, India, Iran, Japan, South Korea, and Taiwan). Ambient particulate material (PM2·5) levels for the year of enrolment (or 1998 if enrolled earlier) were assigned utilizing satellite and sensor-based maps. Cox proportional models were used to examine the association between ambient air pollution and all-cause and cause-specific mortality (all cancer, lung cancer, cardiovascular and lung disease). Models were additionally adjusted for urbanicity (representing urban and built characteristics) and stratified by smoking status in secondary analyses. Country-specific findings were pooled via random-effects meta-analysis. FINDINGS: More than 300,000 participants across six cohorts were included, representing more than 4-million-person years. A positive relationship was observed between a 5 µg/m (Dockery et al., 1993) increase in PM2·5 and cardiovascular mortality (HR: 1·06, 95 % CI: 0.99, 1·13). The additional adjustment for urbanicity resulted in increased associations between PM2.5 and mortality outcomes, including all-cause mortality (1·04, 95 % CI: 0·97, 1·11). Results were generally similar regardless of whether one was a current, never, or ex-smoker. INTERPRETATION: Using satellite and remote sensing technology we showed that associations between PM2.5 and all-cause and cause-specific Hazard Ratios estimated are similar to those reported for U.S. and European cohorts. FUNDING: This project was supported by the Health Effects Institute. Grant number #4963-RFA/18-5. Specific funding support for individual cohorts is described in the Acknowledgements.

Quantifying the natural history of breast cancer.

BACKGROUND: Natural history models of breast cancer progression provide an opportunity to evaluate and identify optimal screening scenarios. This paper describes a detailed Markov model characterising breast cancer tumour progression. METHODS: Breast cancer is modelled by a 13-state continuous-time Markov model. The model differentiates between indolent and aggressive ductal carcinomas in situ tumours, and aggressive tumours of different sizes. We compared such aggressive cancers, that is, which are non-indolent, to those which are non-growing and regressing. Model input parameters and structure were informed by the 1978-1984 Ostergotland county breast screening randomised controlled trial. Overlaid on the natural history model is the effect of screening on diagnosis. Parameters were estimated using Bayesian methods. Markov chain Monte Carlo integration was used to sample the resulting posterior distribution. RESULTS: The breast cancer incidence rate in the Ostergotland population was 21 (95% CI: 17-25) per 10 000 woman-years. Accounting for length-biased sampling, an estimated 91% (95% CI: 85-97%) of breast cancers were aggressive. Larger tumours, 21-50 mm, had an average sojourn of 6 years (95% CI: 3-16 years), whereas aggressive ductal carcinomas in situ took around half a month (95% CI: 0-1 month) to progress to the invasive ≤10 mm state. CONCLUSION: These tumour progression rate estimates may facilitate future work analysing cost-effectiveness and quality-adjusted life years for various screening strategies.

Translational aspects of genetic factors in the prediction of drug response variability: a case study of warfarin pharmacogenomics in a multi-ethnic cohort from Asia.

Genetic markers displaying highly significant statistical associations with complex phenotypes may not necessarily possess sufficient clinical validity to be useful. Understanding the contribution of these markers beyond readily available clinical biomarkers is particularly important in pharmacogenetics. We demonstrate the utility of genetic testing using the example of warfarin in a multi-ethnic setting comprising of three Asian populations that are broadly representative of the genetic diversity for half of the population in the world, especially as distinct interethnic differences in warfarin dose requirements have been previously established. We confirmed the roles of three well-established loci (CYP2C9, VKORC1 and CYP4F2) in explaining warfarin dosage variation in the three Asian populations. In addition, we assessed the relationship between ethnicity and the genotypes of these loci, observing strong correlations at VKORC1 and CYP4F2. Subsequently, we established the additional utility of these genetic factors in predicting warfarin dose beyond ethnicity and clinical biomarkers through performing a series of systematic cross-validation analyses of the relative predictive accuracies of various fixed-dose regimen, clinical and genetic models. Through a pharmacogenetics model for warfarin, we show the importance of genetic testing beyond readily available clinical biomarkers in predicting dose requirements, confirming the role of genetic profiling in personalized medicine.

Mammographic density and its interaction with other breast cancer risk factors in an Asian population.

BACKGROUND: Joint effects of mammographic density and other risk factors on breast cancer risk remain unclear. METHODS: From The Singapore Breast Screening Project, we selected 491 cases and 982 controls. Mammographic density was measured quantitatively. Data analysis was by conditional logistic regression. RESULTS: Density was a significant risk factor, adjusting for other factors. Density of 76-100% had an odds ratio of 5.54 (95% CI 2.38-12.90) compared with 0-10%. Density had significant interactions with body mass index and oral contraceptive use (P=0.02). CONCLUSIONS: Percent density increases breast cancer risk in addition to effects of other risk factors, and modifies the effects of BMI and OCs.

Parental perspectives towards sugar-sweetened beverages and polices: a qualitative study.

PURPOSE: This qualitative study aimed to understand parental perception of (1) sugar-sweetened beverages (SSB) and implications of SSB on health; (2) their role in shaping their children's consumption of SSB; (3) the influences on SSB consumption of their children; and (4) potential government policies targeted at controlling SSB consumption. METHODS: English-speaking parents of pre-schoolers aged 2-6 years were recruited. Semi-structured interviews based on the knowledge, attitude, practice framework were conducted, and transcripts were subjected to thematic analysis based on inductive approaches. Recruitment continued until data saturation was reached. RESULTS: Twenty parents participated in the study and themes addressing the objectives identified. (1) There were misconceptions regarding the healthfulness of certain non-packaged SSB such as traditional remedies and juices. Some were unaware about the association between SSB and dental caries. (2) The need to reduce and restrict sugar consumption for overall and oral health reasons was well-recognised, but the extent of control varied. (3) Multiple stakeholders including pre-schools, grandparents and domestic helpers were involved in shaping children's diet. Children's sugar intake was also influenced by environmental factors, such as the ubiquitously available SSB, targeted marketing and high cost of healthy alternatives. (4) Participants were less accepting towards SSB taxation than the ban of SSB sales. CONCLUSION: Despite the awareness of the types of SSBs and the general/oral health implications of sugar consumption, misconceptions exist. Although most parents possessed the knowledge and attitude, this did not translate into the practice of reducing sugar consumption in their children. There was no SSB reduction policy that had overwhelming acceptability.

Risks of second primary cancer among patients with major histological types of lung cancers in both men and women.

BACKGROUND: Patterns of second primary cancers (SPCs) following first primary lung cancers (FPLCs) may provide aetiological insights into FPLC. METHODS: Cases of FPLCs in 13 cancer registries in Europe, Australia, Canada, and Singapore were followed up from the date of FPLC diagnosis to the date of SPC diagnosis, date of death, or end of follow-up. Standardised incidence ratios (SIRs) were calculated to estimate the magnitude of SPC development following squamous cell carcinoma (SCC), small cell lung carcinoma (SCLC), and adenocarcinoma (ADC). RESULTS: Among SCC patients, male SIR=1.58 (95% confidence interval (CI)=1.50-1.66) and female SIR=2.31 (1.94-2.72) for smoking-related SPC. Among SCLC patients, the respective ratios were 1.39 (1.20-1.60) and 2.28 (1.73-2.95), and among ADC patients, they were 1.73 (1.57-1.90) and 2.24 (1.91-2.61). We also observed associations between first primary lung ADC and second primary breast cancer in women (SIR=1.25, 95% CI=1.05-1.48) and prostate cancer (1.56, 1.39-1.79) in men. CONCLUSION: The FPLC patients carried excess risks of smoking-related SPCs. An association between first primary lung ADC and second primary breast and ovarian cancer in women at younger age and prostate cancers in men may reflect an aetiological role of hormones in lung ADC.

Effect of childbirth after treatment on long-term survival from breast cancer.

BACKGROUND: This study quantified long-term absolute and relative mortality risks of survivors of breast cancer with subsequent childbirth. METHODS: The Singapore Birth Register (n = 319,437), Swedish Multi-Generation Register (n = 11 million) and population-based cancer registries were linked to identify 492 women with childbirth after breast cancer. For these women, cumulative mortality risks and standardized mortality ratios (SMRs) were calculated and compared with those of 8529 women aged less than 40 years with breast cancer without subsequent childbirth, and with those predicted by Adjuvant! Online. RESULTS: Women with subsequent childbirth had a lower 15-year cumulative overall mortality rate than other women with breast cancer (16.8 (95 per cent confidence interval (c.i.) 13.3 to 20.9) versus 40.7 (39.5 to 41.9) per cent), but a higher relative mortality risk than the background population (SMR 13.6, 95 per cent c.i. 10.6 to 17.3). Mortality risks decreased significantly with increasing interval between diagnosis and subsequent childbirth. Mean 10-year cumulative mortality risks of women with subsequent childbirth were within the range of 10-year mortality predicted by Adjuvant! Online for women with T1 N0 tumours in otherwise perfect health. CONCLUSION: This study reinforced the view that pregnancy after breast cancer is not detrimental to survival. However, women who gave birth after this diagnosis had substantially higher mortality risks than young women in the general population. This information may be a valuable addition to routine mortality estimates.

Microarray analysis of multiple candidate genes and associated plasma proteins for nephropathy secondary to type 2 diabetes among Chinese individuals.

AIMS/HYPOTHESIS: Evolving research suggests that common and rare alleles jointly constitute the genetic landscape of complex disease. We studied the association between 43 pathway-related candidate genes with 'intermediate phenotype' (i.e. corresponding plasma protein) and diabetic nephropathy in a customised microarray of 1,536 SNPs. METHODS: In this case-control study of type 2 diabetic Chinese individuals with and without diabetic nephropathy, cases (n = 545) were defined on the basis of a spot urinary albumin/creatinine ratio (ACR) > 113 mg/mmol; the value for controls (n = 503) was ACR < 3.3 mg/mmol. Genotyping was performed using Illumina GoldenGate assay. RESULTS: No single nucleotide polymorphism (SNP) remained significant in single locus analysis after correction for multiple testing. Therefore, we explored the best approximately 1% SNPs. Of these 13 SNPs, four clustered to a 5' end NADPH oxidase homologue 4 (NOX4) haplotype (GGCC frequency = 0.776) with estimated OR for diabetic nephropathy of 2.05 (95% CI 1.04-4.06) (heterozygous) and 2.48 (1.27-4.83) (homozygous) (p = 0.0055). The haplotype was correlated with plasma Cu/Zn superoxide dismutase (SOD) concentration, suggesting increased oxidative burden. Endothelin-1 SNP (rs1476046G>A, frequency = 0.252) was correlated with plasma C-terminal pro-endothelin-1 concentrations with an estimated OR for diabetic nephropathy of (heterozygous) 1.26 (0.96-1.66) and (homozygous) 1.87 (1.13-3.12) (p = 0.0072). Nitric oxide synthase 1 (NOS1) 5' haplotype (TGTC frequency = 0.38) also revealed a suggestive association with diabetic nephropathy: heterozygous 1.26 (0.95-1.67), homozygous 1.57 (1.04-2.35) (p = 0.0073). A rare NADPH oxidase homologue 1 (NOX1)-coding non-synonymous SNP (Arg315His, frequency = 0.006) was found exclusively among cases. CONCLUSIONS/INTERPRETATION: Our preliminary observations suggest that common haplotypes from NOX4 and endothelin-1 SNP correlated with plasma Cu/Zn SOD and C-terminal pro-endothelin-1 concentrations, respectively, and might have conferred diabetic nephropathy susceptibility. Common NOS1 and rare NOX1 variants also revealed a suggestive association with diabetic nephropathy. Future studies to validate our observation are needed.

The Long-Term Impact of Functional Disability on Hospitalization Spending in Singapore.

Singapore is one of the fastest-aging populations due to increased life expectancy and lowered fertility. Lifestyle changes increase the burden of chronic diseases and disability. These have important implications for social protection systems. The goal of this paper is to model future functional disability and healthcare expenditures based on current trends. To project the health, disability and hospitalization spending of future elders, we adapted the Future Elderly Model (FEM) to Singapore. The FEM is a dynamic Markov microsimulation model developed in the US. Our main source of population data was the Singapore Chinese Health Study (SCHS) consisting of 63,000 respondents followed up over three waves from 1993 to 2010. The FEM model enables us to investigate the effects of disability compounded over the lifecycle and hospitalization spending, while adjusting for competing risk of multi-comorbidities. Results indicate that by 2050, 1 in 6 elders in Singapore will have at least one ADL disability and 1 in 3 elders will have at least one IADL disability, an increase from 1 in 12 elders and 1 in 5 elders respectively in 2014. The highest prevalence of functional disability will be in those aged 85 years and above. Lifetime hospitalization spending of elders aged 55 and above is US$24,400 (30.2%) higher among people with functional disability compared to those without disability. Policies that successfully tackle diabetes and promote healthy living may reduce or delay the onset of disability, leading to potential saving. In addition, further technological improvements may reduce the financial burden of disability.

Risk of second malignant neoplasms after childhood central nervous system malignant tumours: an international study.

PURPOSE: The aim of this study was to assess the risk of second malignant neoplasms (SMNs) other than central nervous system (CNS) neoplasms after childhood CNS cancer in an international multicentre study. METHODS: Individual data on cases of CNS cancer in children (0-14 years) and on subsequent SMNs were obtained from 13 population-based cancer registries contributing data for different time periods in 1943-2000. Standardised incidence ratios (SIRs) with 95% confidence intervals (CI), absolute excess risk and cumulative incidence of SMNs were computed. RESULTS: We observed 43 SMNs in 8431 CNS cancer survivors. The SIR was 10.6 (4.85-20.1) for thyroid cancer (nine cases), 2.75 (1.01-5.99) for leukaemia (six cases) and 2.47 (0.90-5.37) for lymphoma (six cases). The SIRs were highest in the first 10 years after CNS cancer diagnosis. The cumulative incidence of non-CNS SMNs was 3.30% (0.95-5.65%) within 45 years after a CNS cancer diagnosis. Within 15 years, the cumulative incidence was highest for cases diagnosed after 1980 (0.56%, 95% CI: 0.29-0.82%). CONCLUSION: This population-based study indicates that about one every 180 survivors of a childhood CNS cancer will develop a non-CNS SMN within the following 15 years. The excess is higher after glioma and embryonal malignant tumour than after another CNS tumour.

A gentle introduction to SNP analysis: resources and tools.

Bioinformatics is the use of informatics tools and techniques in the study of molecular biology, genetic, or clinical data. The field of bioinformatics has expanded tremendously to cope with the large expansion of information generated by the mouse and human genome projects, as newer generations of computers that are much more powerful have emerged in the commercial market. It is now possible to employ the computing hardware and software at hand to generate novel methodologies in order to link data across the different databanks generated by these international projects and derive clinical and biological relevance from all of the information gathered. The ultimate goal would be to develop a computer program that can provide information correlating genes, their single nucleotide polymorphisms (SNPs), and the possible structural and functional effects on the encoded proteins with relation to known information on complex diseases with great ease and speed. Here, the recent developments of available software methods to analyze SNPs in relation to complex diseases are reviewed with emphasis on the type of predictions on protein structure and functions that can be made. The need for further development of comprehensive bioinformatics tools that can cope with information generated by the genomics communities is emphasized.

Association of renal function and delta-aminolevulinic acid dehydratase polymorphism among Vietnamese and Singapore workers exposed to inorganic lead.

OBJECTIVES: To investigate the effect of delta-aminolevulinic acid dehydratase (ALAD) polymorphisms on the association between blood lead and renal function among Vietnamese and Singaporean workers who were exposed to low to medium levels of inorganic lead, and to study the distribution of ALAD polymorphism among Vietnamese, Chinese, Malays and Indians. METHODS: A total of 459 male and female workers were studied. Blood and urine were collected for each worker in order to determine ALAD genotype, blood lead, and urinary delta-aminolevulinic acid (ALAU). Renal function tests included urine albumin (Ualb), urine beta2 microglobulin (Ubeta2m), urinary alpha1 microglobulin (Ualpha1m), N-acetyl-glucosaminidas (NAG), and urine retinol blinding protein (RBP). A multiple regression model with interaction term was applied to fit the entire data and to explore the modifying effect of ALAD polymorphism on the relation of blood lead to each renal function parameter. RESULTS: ALAD1-1 was the predominant genotype for all the ethnic groups while ALAD2-2 was the rarest. The frequency of ALAD2 allele was higher among Malays (8.8%) and Indians (10.6%) compared to the Chinese (5.0%) and Vietnamese (4.3%). The geometric mean of blood lead for all workers was 19.0 microg/dl. The models for Ubeta2m, Ualpha1m, and NAG showed that the ALAD1-2/2-2 group had higher beta coefficients than the ALAD1-1 group. Corresponding to 10 microg/dl blood lead, ALAD1-1 homozygotes had an increment of 1.288 microg/g Cr, 1.175 mg/g Cr, and 1.995 U/g Cr for Ubeta2m, Ualpha1m, and NAG, respectively. ALAD1-2/2-2 subjects had higher increments of 3.802 microg/g Cr, 2.138 mg/g Cr, and 3.89 U/g Cr for Ubeta2m, Ualpha1m, and NAG, respectively. CONCLUSION: The frequency of the ALAD2 allele is as low in Vietnamese workers as in Chinese. Workers with the ALAD2 allele appeared more susceptible to the effects of lead (especially at higher levels) on renal function.

Role of urinary screening programmes in children in the prevention of chronic kidney disease.

INTRODUCTION: This article reviews published literature on the usefulness of population-based urinary screening in the Asian paediatric population. METHODS: Articles were found in the Medline database using the key words "paediatrics", "urine screening", "proteinuria", "haematuria" and "population". The Asian countries which had carried out population-based urinary screening of the paediatric population included Taiwan, Japan and Korea. One study was found on urinary screening in a select population in Malaysia. Preliminary results of the urinary screening of school children in Singapore are presented and compared with the results found in the above-mentioned countries. RESULTS: Overall, the proportion of children found to have urinary abnormalities ranged from less than 0.1% of the population screened to almost 50% of a select cohort referred from the screening programmes for the evaluation of urinary abnormalities. In the pilot Singapore school screening programme, the prevalence of clinically significant proteinuria was 1.25 per 1000 children screened. Multivariate analysis showed that low body weight was associated with a 1.8-fold greater risk for proteinuria. The major cause of haematuria and proteinuria in those studies where renal biopsies were performed was glomerulonephritis. The Taiwanese experience also showed a reduction in the incidence of end-stage renal failure diagnosed in children after the onset of urine screening. CONCLUSION: These studies showed that urinary screening programmes in school children allow the early detection of disease. The cost-benefit ratio for specific populations should be determined before the implementation of such programmes.

Anthropometrics indices of obesity, and all-cause and cardiovascular disease-related mortality, in an Asian cohort with type 2 diabetes mellitus.

AIM: The study investigated the relationship of general (body mass index [BMI]) and central (waist circumference [WC]; waist-hip ratio [WHipR]; waist-height ratio [WHeightR]) adiposity with all-cause and cardiovascular disease (CVD)-related mortality in an Asian population with diabetes. METHODS: A total of 13,278 participants with type 2 diabetes mellitus (T2DM) recruited from public-sector primary-care and specialist outpatients clinics in Singapore were followed-up for a median duration of 2.9 years, during which time there were 524 deaths. Cox proportional-hazards regression and competing-risk models were used to obtain hazard ratios (HRs) for anthropometric variables of all-cause and CVD-related mortality. RESULTS: After adjusting for BMI, the highest quintiles of WC, WHipR and WHeightR were all positively associated with mortality compared with the lowest quintiles, with WHeightR exhibiting the largest effect sizes [all-cause mortality HR: 2.13, 95% confidence interval (CI): 1.33-3.42; CVD-related mortality HR: 3.42, 95% CI: 1.62-7.19]. Being overweight but not obese (BMI:≥23.0 but<27.5kg/m(2)) was associated with a decreased risk of CVD-related mortality in those aged≥65 years (HR: 0.47, 95% CI: 0.29-0.75), but not in those aged<65 years (HR: 1.11, 95% CI: 0.49-2.50). CONCLUSION: Overweight, but not obesity, was associated with a reduction in risk of mortality. This was seen in T2DM patients aged≥65 years, but not in those younger than this. At the same BMI, having higher central-obesity indices such as WC, WHipR and WHeightR also increased the risk of mortality.

APOE polymorphism and lipid profile in three ethnic groups in the Singapore population.

BACKGROUND: Serum lipid concentrations are modulated by environmental factors such as exercise, alcohol intake, smoking, obesity and dietary intake and genetic factors. Polymorphisms at the Apolipoprotein E (APOE) locus have consistently shown a significant association with total and LDL-cholesterol (LDL-C). However, their impact on HDL-cholesterol (HDL-C) may be population dependent. Having three major ethnic groups within a similar social environment allows us to study the role of genetics and their interactions with lifestyle factors on the serum lipid profile and coronary risk in Asians. METHODS: This study included 1740 males (1146 Chinese, 327 Malays and 267 Asian Indians) and 1950 females (1329 Chinese, 360 Malays and 261 Asian Indians) with complete data on anthropometric indices, fasting lipids, smoking status, alcohol consumption, exercise frequency and genotype at the APOE locus. RESULTS: Malays and Asian Indians were more obese compared with the Chinese. Smoking was uncommon in all females but Malay males had significantly higher prevalence of smokers. Malays had the highest LDL-C whilst Indians had the lowest HDL-C, The epsilon 3 allele was the most frequent allele in all three ethnic groups. Malays had the highest frequency of epsilon 4 (0.180 and 0.152) compared with Chinese (0.085 and 0.087) and Indians (0.108 and 0.075) in males and females, respectively. The epsilon 2 allele was the least common in Asian Indians. Total cholesterol (TC) and LDL-C was highest in epsilon 4 carriers and lowest in epsilon 2 carriers. The reverse was seen in HDL-C with the highest levels seen in epsilon 2 subjects. The association between ethnic group and HDL-C differed according to APOE genotype and gender. Asian Indians had the lowest HDL-C for each APOE genotype except in Asian Indian males with epsilon 2, where HDL-C concentrations were intermediate between Chinese and Malays. CONCLUSION: Ethnic differences in lipid profile could be explained in part by the higher prevalence of epsilon 4 in the Malays. Ethnicity may influence the association between APOE genotypes and HDL-C. APOE genotype showed no correlation with HDL-C in Malay males whereas the association in Asian Indians was particularly marked. Further studies of interactions between genes and environmental factors will contribute to the understanding of differences of coronary risk amongst ethnic groups.