Displaying publications 1 - 20 of 43 in total

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  1. Nongpiur ME, Khor CC, Jia H, Cornes BK, Chen LJ, Qiao C, et al.
    PLoS Genet, 2014 Mar;10(3):e1004089.
    PMID: 24603532 DOI: 10.1371/journal.pgen.1004089
    Anterior chamber depth (ACD) is a key anatomical risk factor for primary angle closure glaucoma (PACG). We conducted a genome-wide association study (GWAS) on ACD to discover novel genes for PACG on a total of 5,308 population-based individuals of Asian descent. Genome-wide significant association was observed at a sequence variant within ABCC5 (rs1401999; per-allele effect size =  -0.045 mm, P = 8.17 × 10(-9)). This locus was associated with an increase in risk of PACG in a separate case-control study of 4,276 PACG cases and 18,801 controls (per-allele OR = 1.13 [95% CI: 1.06-1.22], P = 0.00046). The association was strengthened when a sub-group of controls with open angles were included in the analysis (per-allele OR = 1.30, P = 7.45 × 10(-9); 3,458 cases vs. 3,831 controls). Our findings suggest that the increase in PACG risk could in part be mediated by genetic sequence variants influencing anterior chamber dimensions.
  2. Khor CC, Do T, Jia H, Nakano M, George R, Abu-Amero K, et al.
    Nat Genet, 2016 May;48(5):556-62.
    PMID: 27064256 DOI: 10.1038/ng.3540
    Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study (GWAS) followed by replication in a combined total of 10,503 PACG cases and 29,567 controls drawn from 24 countries across Asia, Australia, Europe, North America, and South America. We observed significant evidence of disease association at five new genetic loci upon meta-analysis of all patient collections. These loci are at EPDR1 rs3816415 (odds ratio (OR) = 1.24, P = 5.94 × 10(-15)), CHAT rs1258267 (OR = 1.22, P = 2.85 × 10(-16)), GLIS3 rs736893 (OR = 1.18, P = 1.43 × 10(-14)), FERMT2 rs7494379 (OR = 1.14, P = 3.43 × 10(-11)), and DPM2-FAM102A rs3739821 (OR = 1.15, P = 8.32 × 10(-12)). We also confirmed significant association at three previously described loci (P < 5 × 10(-8) for each sentinel SNP at PLEKHA7, COL11A1, and PCMTD1-ST18), providing new insights into the biology of PACG.
  3. Vithana EN, Khor CC, Qiao C, Nongpiur ME, George R, Chen LJ, et al.
    Nat Genet, 2012 Oct;44(10):1142-1146.
    PMID: 22922875 DOI: 10.1038/ng.2390
    Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study including 1,854 PACG cases and 9,608 controls across 5 sample collections in Asia. Replication experiments were conducted in 1,917 PACG cases and 8,943 controls collected from a further 6 sample collections. We report significant associations at three new loci: rs11024102 in PLEKHA7 (per-allele odds ratio (OR)=1.22; P=5.33×10(-12)), rs3753841 in COL11A1 (per-allele OR=1.20; P=9.22×10(-10)) and rs1015213 located between PCMTD1 and ST18 on chromosome 8q (per-allele OR=1.50; P=3.29×10(-9)). Our findings, accumulated across these independent worldwide collections, suggest possible mechanisms explaining the pathogenesis of PACG.
  4. Lee SV, Tai ES, Mutalib AR, Khairani-Bejo S, Bahaman AR
    Trop Biomed, 2011 Dec;28(3):497-505.
    PMID: 22433877 MyJurnal
    A simple and reliable tool for the early diagnosis of leptospirosis is urgently needed. We report the development of a lyophilized reagent-based polymerase chain reaction (PCR) assay targeting lipL32 gene, which is present only in pathogenic leptospires. To determine the effectiveness of the newly developed assay in the early diagnosis of leptospirosis, the sensitivity and specificity was evaluated. In simulated clinical samples, the assay was able to detect 10² and 10³ leptospires/ml in spiked urine and blood samples, respectively. In experimentally infected animals, leptospiral DNA could be detected in blood and lung samples as early as Day 1 post infection. This assay was also shown to be stable and remained sensitive for up to five months at ambient temperature. Hence, this lyophilized reagent-based PCR assay with high specificity, sensitivity and stability would provide a simple, rapid and reliable method in diagnosing acute leptospirosis, especially in the field of veterinary medicine.
  5. Tan CE, Emmanuel SC, Tan BY, Tai ES, Chew SK
    Atherosclerosis, 2001 Mar;155(1):179-86.
    PMID: 11223440 DOI: 10.1016/s0021-9150(00)00534-7
    AIMS: To compare cardiovascular risk factors in diabetic subjects of different ethnic groups, and between new and known diabetic subjects, in the Singapore National Health Survey '92.

    METHODS: Disproportionate stratified sampling followed by systematic sampling were used in 3568 (total) respondents of whom 2743 were non-diabetics, 179 newly diagnosed diabetics and 150 known diabetics. Amongst the diabetics, there were 185 Chinese, 66 Malays and 78 Asian Indians. Diagnosis of diabetes mellitus (DM) was based on the 2 h glucose alone, after a 75 g oral glucose tolerance test. Blood pressure (BP), lipid profile, glucose, insulin and anthropometric indices were obtained from all subjects.

    RESULTS: Subjects with diabetes (new and known) exhibited significantly higher triglyceride (TG), lower high density lipoprotein cholesterol (HDL-C) and low density lipoprotein (LDL)/apolipoprotein B (apo B) ratio (LDL size) compared with normoglycaemic subjects. They were more obese (generalised and central) and had higher systolic and diastolic BP. There was no difference in lipid risk factors between the two groups with diabetes although those with new diabetes were more obese whilst those with known diabetes had higher fasting glucose. Amongst subjects with diabetes, there were no significant differences between ethnic groups in TG, HDL-C, LDL/apo B ratio, or waist to hip ratio (WHR). Female Malays with diabetes had higher total cholesterol and were more obese whilst male Asian Indians with diabetes had higher fasting insulin.

    CONCLUSION: Asian Indians had lower HDL-C and LDL/apo B ratio than Chinese or Malays amongst normoglycaemic subjects. However, these differences between ethnic groups were not seen in subjects with DM.
  6. Ma RC, Hu C, Tam CH, Zhang R, Kwan P, Leung TF, et al.
    Diabetologia, 2013 Jun;56(6):1291-305.
    PMID: 23532257 DOI: 10.1007/s00125-013-2874-4
    AIMS/HYPOTHESIS: Most genetic variants identified for type 2 diabetes have been discovered in European populations. We performed genome-wide association studies (GWAS) in a Chinese population with the aim of identifying novel variants for type 2 diabetes in Asians.

    METHODS: We performed a meta-analysis of three GWAS comprising 684 patients with type 2 diabetes and 955 controls of Southern Han Chinese descent. We followed up the top signals in two independent Southern Han Chinese cohorts (totalling 10,383 cases and 6,974 controls), and performed in silico replication in multiple populations.

    RESULTS: We identified CDKN2A/B and four novel type 2 diabetes association signals with p 

  7. Parvaresh Rizi E, Teo Y, Leow MK, Venkataraman K, Khoo EY, Yeo CR, et al.
    J Clin Endocrinol Metab, 2015 11;100(11):4249-56.
    PMID: 26308293 DOI: 10.1210/jc.2015-2639
    CONTEXT: Among Asian ethnic groups, Chinese or Malays are more insulin sensitive than South Asians, in particular in lean individuals. We have further reported that body fat partitioning did not explain this ethnic difference in insulin sensitivity.

    OBJECTIVE: We examined whether adipocytokines might explain the ethnic differences in the relationship between obesity and insulin resistance among the three major ethnic groups in Singapore.

    DESIGN AND PARTICIPANTS: This was a cross-sectional study of 101 Chinese, 82 Malays, and 81 South Asian men. Insulin sensitivity index (ISI) was measured using hyperinsulinemic euglycemic clamp. Visceral (VAT) and subcutaneous adipose tissue (SAT) volumes were quantified using magnetic resonance imaging.

    MAIN OUTCOME MEASURES: Plasma total and high-molecular-weight adiponectin, leptin, visfatin, apelin, IL-6, fibroblast growth factor 21 (FGF21), retinol binding protein-4 (RBP 4), and resistin were measured using enzyme-linked immunoassays.

    RESULTS: Principle component (PC) analysis on the adipocytokines identified three PCs, which explained 49.5% of the total variance. Adiponectin loaded negatively, and leptin and FGF21 loaded positively onto PC1. Visfatin, resistin, and apelin all loaded positively onto PC2. IL-6 loaded positively and RBP-4 negatively onto PC3. Only PC1 was negatively associated with ISI in all ethnic groups. In the path analysis, SAT and VAT were negatively associated with ISI in Chinese and Malays without significant mediatory role of PC1. In South Asians, the relationship between VAT and ISI was mediated partly through PC1, whereas the relationship between SAT and ISI was mediated mainly through PC1.

    CONCLUSIONS: The relationships between abdominal obesity, adipocytokines and insulin sensitivity differ between ethnic groups. Adiponectin, leptin, and FGF21 play a mediating role in the relationship between abdominal adiposity and insulin resistance in South Asians, but not in Malays or Chinese.

  8. Venkataraman K, Kao SL, Thai AC, Salim A, Lee JJ, Heng D, et al.
    Diabet Med, 2012 Jul;29(7):911-7.
    PMID: 22283416 DOI: 10.1111/j.1464-5491.2012.03599.x
    AIMS: To study whether HbA(1c) , and its relationship with fasting plasma glucose, was significantly different among Chinese, Malays and Indians in Singapore.

    METHODS: A sample of 3895 individuals without known diabetes underwent detailed interview and health examination, including anthropometric and biochemical evaluation, between 2004 and 2007. Pearson's correlation, analysis of variance and multiple linear regression analyses were used to examine the influence of ethnicity on HbA(1c) .

    RESULTS: As fasting plasma glucose increased, HbA(1c) increased more in Malays and Indians compared with Chinese after adjustment for age, gender, waist circumference, serum cholesterol, serum triglyceride and homeostasis model assessment of insulin resistance (P-interaction < 0.001). This translates to an HbA(1c) difference of 1.1 mmol/mol (0.1%, Indians vs. Chinese), and 0.9 mmol/mol (0.08%, Malays vs. Chinese) at fasting plasma glucose 5.6 mmol/l (the American Diabetes Association criterion for impaired fasting glycaemia); and 2.1 mmol/mol (0.19%, Indians vs. Chinese) and 2.6 mmol/mol (0.24%, Malays vs. Chinese) at fasting plasma glucose 7.0 mmol/l, the diagnostic criterion for diabetes mellitus.

    CONCLUSIONS: Using HbA(1c) in place of fasting plasma glucose will reclassify different proportions of the population in different ethnic groups. This may have implications in interpretation of HbA(1c) results across ethnic groups and the use of HbA(1c) for diagnosing diabetes mellitus.

  9. Chan MY, Tan K, Tan HC, Huan PT, Li B, Phua QH, et al.
    Pharmacogenomics, 2012 Apr;13(5):533-42.
    PMID: 22462746 DOI: 10.2217/pgs.12.24
    AIM, MATERIALS & METHODS: We investigated the functional significance of CYP2C19*2, *3, *17 and PON1 Q192R SNPs in 89 consecutive Asian patients on clopidogrel treatment and the prevalence of functionally significant polymorphisms among 300 Chinese, Malays and Asian Indians.
  10. Foo JN, Tan LC, Liany H, Koh TH, Irwan ID, Ng YY, et al.
    Hum Mol Genet, 2014 Jul 15;23(14):3891-7.
    PMID: 24565865 DOI: 10.1093/hmg/ddu086
    To evaluate the contribution of non-synonymous-coding variants of known familial and genome-wide association studies (GWAS)-linked genes for Parkinson's disease (PD) to PD risk in the East Asian population, we sequenced all the coding exons of 39 PD-related disease genes and evaluated the accumulation of rare non-synonymous-coding variants in 375 early-onset PD cases and 399 controls. We also genotyped 782 non-synonymous-coding variants of these genes in 710 late-onset PD cases and 9046 population controls. Significant enrichment of LRRK2 variants was observed in both early- and late-onset PD (odds ratio = 1.58; 95% confidence interval = 1.29-1.93; P = 8.05 × 10(-6)). Moderate enrichment was also observed in FGF20, MCCC1, GBA and ITGA8. Half of the rare variants anticipated to cause loss of function of these genes were present in healthy controls. Overall, non-synonymous-coding variants of known familial and GWAS-linked genes appear to make a limited contribution to PD risk, suggesting that clinical sequencing of these genes will provide limited information for risk prediction and molecular diagnosis.
  11. Leow MK, Griva K, Choo R, Wee HL, Thumboo J, Tai ES, et al.
    PLoS One, 2013;8(6):e67138.
    PMID: 23826215 DOI: 10.1371/journal.pone.0067138
    BACKGROUND: HRQoL is an important outcome to guide and promote healthcare. Clinical and socioeconomic factors may influence HRQoL according to ethnicity.

    METHODOLOGY: A multiethnic cross-sectional national cohort (N = 7198) of the Singapore general population consisting of Chinese (N = 4873), Malay (N = 1167) and Indian (N = 1158) adults were evaluated using measures of HRQoL (SF-36 version 2), family functioning, health behaviours and clinical/laboratory assessments. Multiple regression analyses were performed to identify determinants of physical and mental HRQoL in the overall population and their potential differential effects by ethnicity. No a priori hypotheses were formulated so all interaction effects were explored.

    PRINCIPAL FINDINGS: HRQoL levels differed between ethnic groups. Chinese respondents had higher physical HRQoL (PCS) than Indian and Malay participants (p<0.001) whereas mental HRQoL (MCS) was higher in Malay relative to Chinese participants (p<0.001). Regressions models explained 17.1% and 14.6% of variance in PCS and MCS respectively with comorbid burden, income and employment being associated with lower HRQoL. Age and family were associated only with MCS. The effects of gender, stroke and musculoskeletal conditions on PCS varied by ethnicity, suggesting non-uniform patterns of association for Chinese, Malay and Indian individuals.

    CONCLUSIONS: Differences in HRQoL levels and determinants of HRQoL among ethnic groups underscore the need to better or differentially target population segments to promote well-being. More work is needed to explore HRQoL and wellness in relation to ethnicity.

  12. Yang PL, Lu Y, Khoo CM, Leow MK, Khoo EY, Teo A, et al.
    J Clin Endocrinol Metab, 2013 Nov;98(11):4516-23.
    PMID: 24037892 DOI: 10.1210/jc.2013-2454
    Chinese men in Singapore have a higher incidence of hip fractures than Malay and Indian men. We investigated whether there were corresponding ethnic differences in peak bone mineral density (BMD) in young men and whether differences in body composition influenced peak BMD.
  13. Shen H, Qi L, Tai ES, Chew SK, Tan CE, Ordovas JM
    Obesity (Silver Spring), 2006 Apr;14(4):656-61.
    PMID: 16741267
    A polymorphism in the promoter region of uncoupling protein 2 gene -866G/A has been associated with its expression levels in adipose tissue, the risk of obesity, and metabolic abnormalities. Our purpose was to examine the associations of -866G/A with body fat and the risk of metabolic syndrome in a random sample of 4018 Asians (1858 men and 2160 women) from three ethnic groups (Chinese, Malay, and Indian). The minor allele frequency of -866G/A polymorphism in South Asians was similar to that in whites. After adjustment for covariates including age, cigarette smoking, and physical activity, the -866A/A genotype was associated with higher waist-to-hip ratio as compared with the wild-type genotype in Chinese and Indian men (p = 0.018 and p = 0.046, respectively). Moreover, Indian men with -866A/A genotype had a significantly increased risk of metabolic syndrome as compared with those homozygous for the wild-type (odds ratio, 2.66; 95% confidence interval, 1.21 to 5.88; p = 0.015). Such a risk was mainly caused by the excess presence of hypertriglyceridemia and central obesity. Our findings indicate that the uncoupling protein 2 gene -866G/A polymorphism may increase the risks of central obesity and metabolic syndrome, with greater effects on Asian men.
  14. Qi L, Tai ES, Tan CE, Shen H, Chew SK, Greenberg AS, et al.
    J Mol Med (Berl), 2005 Jun;83(6):448-56.
    PMID: 15770500
    Perilipin is a lipid droplet surface protein present in adipocytes and steroidogenic cells. We examined five common single nucleotide polymorphisms (SNPs) at the perilipin (PLIN) locus (PLIN 6209C>T, 10171A>T, 11482G>A, 13041A>G, and 14995A>T) to investigate their association with obesity risk. The study population included 4,131 subjects of three ethnic groups (Chinese, Malay, and Indian) from Singapore. The prevalence of obesity in Malays and Indians was much higher than in Chinese. Moreover, in these groups the prevalence of obesity was three times higher in women than in men. Crude analysis indicated that haplotype 11212 (CAAAT) is shared by Malays and Indians and is significantly associated with increased obesity risk as compared to the most common haplotype 21111 (TAGAA): OR 1.65 (95% CI 1.11-2.46) in Malays and 1.94 (95% CI 1.06-3.53) in Indians. No associations between PLIN haplotypes and obesity risk were found in Chinese. To simplify the haplotype analyses we used a subgroup of three SNPs (11482G>A, 13041A>G, and 14995A>T) in positive linkage disequilibrium. These analyses revealed similar associations, showing that haplotypes XX212 (XXAAT) and XX222 (XXAGT) are associated with increased obesity risk in Malays OR 2.04 (95% CI 1.28-3.25) and 2.05 (95% CI 1.35-3.12) respectively, and that haplotype XXX212 (XXAAT) is significantly associated with increased obesity risk in Indians OR 2.16 (95% CI 1.10-4.26) after adjusting for covariates including age, sex, smoking, alcohol consumption, exercise, and diabetes status. Moreover, individual SNP analyses demonstrated that the PLIN 14995A>T SNP is the most informative single genetic marker for the observed haplotype association, being significantly associated with increased obesity risk in both Malays OR 2.28 (95% CI 1.45-3.57) and Indians OR 2.04 (95% CI 1.08-3.64). These results support the role of the PLIN locus as an ethnically dependent modulator of obesity risk in humans.
  15. Tan CE, Tai ES, Tan CS, Chia KS, Lee J, Chew SK, et al.
    Atherosclerosis, 2003 Oct;170(2):253-60.
    PMID: 14612205
    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.

  16. Lim CC, Teo BW, Ong PG, Cheung CY, Lim SC, Chow KY, et al.
    Eur J Prev Cardiol, 2015 Aug;22(8):1018-26.
    PMID: 24857889 DOI: 10.1177/2047487314536873
    BACKGROUND: Few studies have examined the impact of chronic kidney disease (CKD) on adverse cardiovascular outcomes and deaths in Asian populations. We evaluated the associations of CKD with cardiovascular disease (CVD) and all-cause mortality in a multi-ethnic Asian population.
    DESIGN: Prospective cohort study of 7098 individuals who participated in two independent population-based studies involving Malay adults (n = 3148) and a multi-ethnic cohort of Chinese, Malay and Indian adults (n = 3950).
    METHODS: CKD was assessed from CKD-EPI estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). Incident CVD (myocardial infarction, stroke and CVD mortality) and all-cause mortality were identified by linkage with national disease/death registries.
    RESULTS: Over a median follow-up of 4.3 years, 4.6% developed CVD and 6.1% died. Risks of both CVD and all-cause mortality increased with decreasing eGFR and increasing albuminuria (all p-trend <0.05). Adjusted hazard ratios (HR (95% confidence interval)) of CVD and all-cause mortality were: 1.54 (1.05-2.27) and 2.21 (1.67-2.92) comparing eGFR <45 vs ≥60; 2.81 (1.49-5.29) and 2.34 (1.28-4.28) comparing UACR ≥300 vs <30. The association between eGFR <60 and all-cause mortality was stronger among those with diabetes (p-interaction = 0.02). PAR of incident CVD was greater among those with UACR ≥300 (12.9%) and that of all-cause mortality greater among those with eGFR <45 (16.5%).
    CONCLUSIONS: In multi-ethnic Asian adults, lower eGFR and higher albuminuria were independently associated with incident CVD and all-cause mortality. These findings extend previously reported similar associations in Western populations to Asians and emphasize the need for early detection of CKD and intervention to prevent adverse outcomes.
  17. Chiang PP, Lamoureux EL, Shankar A, Tai ES, Wong TY, Sabanayagam C
    BMC Public Health, 2013;13:730.
    PMID: 23919264 DOI: 10.1186/1471-2458-13-730
    BACKGROUND: Prehypertension has been shown to be an early risk factor of cardiovascular disease (CVD). We investigated the prevalence and pattern of cardiometabolic risk factors in prehypertension in three ethnic Asian populations in Singapore.
    METHODS: We examined data from Chinese (n=1177), Malay (n=774), and Indian (n=985) adults aged 40-80 years who participated in three independent population based studies conducted from 2004-2011 in Singapore who were free of diabetes, hypertension and previous CVD. Prehypertension was defined as systolic blood pressure (BP) 120-139 mm Hg or diastolic BP 80-89 mm Hg. Random blood glucose, glycated haemoglobin (HbA1c), body mass index (BMI), triglycerides, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol were examined as indicators of adverse cardiometabolic profile. The association between metabolic variables and prehypertension was examined using logistic regression models adjusting for potential confounders.
    RESULTS: The prevalence of prehypertension was 59.8% (Chinese), 68.9% (Malays) and 57.7% Indians. Higher levels of blood glucose, HbA1c and BMI were significantly associated with prehypertension in all three ethnic groups, odds ratio (95% confidence interval) of prehypertension in Chinese, Malays and Indians were: 1.42 (1.10, 1.83), 1.53 (1.05, 2.24), 1.49 (1.13, 1.98) for high-glucose; 3.50 (1.01, 12.18), 3.72 (1.29, 10.75), 2.79 (1.31, 5.94) for high-HbA1c; 1.86 (1.34, 2.56), 2.96 (2.10, 4.18), 1.68 (1.28, 2.20) for high-BMI. In addition, higher levels of LDL cholesterol in Chinese and higher levels of triglycerides were significantly associated with prehypertension. These associations persisted when metabolic variables were analysed as continuous variables.
    CONCLUSIONS: Higher levels of blood glucose, HbA1c and BMI were associated with prehypertension in all three ethnic groups in Singapore. Screening for prehypertension and lifestyle modifications could potentially reduce the burden of CVD in otherwise healthy Asian adults living in Singapore.
  18. Tai ES, Sim XL, Ong TH, Wong TY, Saw SM, Aung T, et al.
    J Lipid Res, 2009 Mar;50(3):514-520.
    PMID: 18987386 DOI: 10.1194/jlr.M800456-JLR200
    We conducted a cross-sectional study of Malay participants aged 40-80 years (n = 2,932) to examine the associations between polymorphisms at newly identified, lipid-associated loci with blood lipid levels and prevalent cardiovascular disease (CVD) in a Malay population in Asia. A polymorphism adjacent to the TRIB1 locus (rs17321515) was associated with elevated total cholesterol and LDL-cholesterol (LDL-C) after adjustment for age and sex (both P values <0.007) and with increased risk of coronary heart disease and CVD [odds ratio (OR) 1.23, 95% confidence interval (95% CI) 1.03-1.46; and OR 1.2, 95% CI 1.02-1.42, respectively] under an additive model of inheritance. In addition, using recessive models of inheritance, polymorphisms on chromosome 19 adjacent to the CILP2 and PBX4 loci (rs16996148) and on chromosome 1 at the GALNT2 locus (rs4846914) were associated with elevated HDL-C (P = 0.005) and lower LDL-C (P = 0.048), respectively. Although novel, the former is consistent with the association between this polymorphism and lower blood triglycerides observed in the initial studies conducted in populations of European ancestry. Neither showed statistically significant association with CVD. These observations should form the basis of further investigation to identify the causative polymorphisms at this locus, and also to understand the mechanistic roles that this protein may play in lipoprotein metabolism in Asians and other populations.
  19. Tai ES, Corella D, Deurenberg-Yap M, Cutter J, Chew SK, Tan CE, et al.
    J Nutr, 2003 Nov;133(11):3399-408.
    PMID: 14608050 DOI: 10.1093/jn/133.11.3399
    We have previously reported an interaction between -514C>T polymorphism at the hepatic lipase (HL) gene and dietary fat on high-density lipoprotein-cholesterol (HDL-C) metabolism in a representative sample of white subjects participating in the Framingham Heart Study. Replication of these findings in other populations will provide proof for the relevance and consistency of this marker as a tool for risk assessment and more personalized cardiovascular disease prevention. Therefore, we examined this gene-nutrient interaction in a representative sample of Singaporeans (1324 Chinese, 471 Malays and 375 Asian Indians) whose dietary fat intake was recorded by a validated questionnaire. When no stratification by fat intake was considered, the T allele was associated with higher plasma HDL-C concentrations (P = 0.001), higher triglyceride (TG) concentrations (P = 0.001) and higher HDL-C/TG ratios (P = 0.041). We found a highly significant interaction (P = 0.001) between polymorphism and fat intake in determining TG concentration and the HDL-C/TG ratio (P = 0.001) in the overall sample even after adjustment for potential confounders. Thus, TT subjects showed higher TG concentrations only when fat intake supplied >30% of total energy. This interaction was also found when fat intake was considered as continuous (P = 0.035). Moreover, in the upper tertile of fat intake, TT subjects had 45% more TG than CC individuals (P < 0.01). For HDL-C concentration, the gene-diet interaction was significant (P = 0.015) only in subjects of Indian origin. In conclusion, our results indicate that there are differences in the association of -514C>T polymorphism with plasma lipids according to dietary intake and ethnic background. Specifically, the TT genotype is associated with a more atherogenic lipid profile when subjects consume diets with a fat content > 30%.
  20. Lee J, Ma S, Heng D, Chew S, Hughes K, Tai E
    J Hum Hypertens, 2008 Jul;22(7):468-74.
    PMID: 18337755 DOI: 10.1038/jhh.2008.16
    The current hypertension (HTN) guidelines recommend the assessment of other cardiovascular disease (CVD) risk factors in individuals with HTN for further management. Few studies in Asian populations have been published to identify the outcome of individuals with HTN and other CVD risk factors. This study aims to assess the effect of HTN alone, and in combination with other CVD risk factors on all-cause and CVD mortality. Three cross-sectional studies carried out in Singapore (baseline 1982--1995) consisting of 5830 persons were grouped by the absence or presence of HTN and CVD risk factors. They were followed-up (mean 14.1 years) by linkage with the National Death Register. Cox's proportional hazards model was used to obtain adjusted hazard ratios (HRs) for risk of mortality. HTN individuals with either <2 CVD risk factors (adjusted HR 1.4; 95% confidence interval (CI) 1.0-1.8) or > or =2 CVD risk factors (adjusted HR 2.3; 95% CI 1.9-3.0) were at increased risk of all-cause mortality compared to normotensive individuals. The findings were similar for CVD mortality. HTN individuals who also smoked or had diabetes were at highest risk of all-cause mortality, whereas those with elevated total cholesterol/high-density lipoprotein cholesterol, smoked or diabetes had the highest risk for CVD mortality. These findings show that in HTN individuals it is important to assess the presence of other CVD risk factors and manage accordingly.
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