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Homeostasis model assessment in a population with mixed ethnicity: the 1992 Singapore National Health Survey

Tai ES, Lim SC, Chew SK, Tan BY, Tan CE

Diabetes Res Clin Pract, 2000 Aug;49(2-3):159-68.
PMID: 10963828 DOI: 10.1016/s0168-8227(00)00152-2

We studied insulin resistance and beta-cell function with reference to ethnic group, glucose tolerance and other coronary artery disease risk factors in a cross section of the Singapore population which comprises Chinese, Malays and Asian Indians. 3568 individuals aged 18-69 were examined. Blood pressure, anthropometric data, blood lipids, glucose and insulin were assayed in the fasting state. Glucose and serum insulin were measured 2 h after an oral glucose challenge. Insulin resistance and beta-cell function were calculated using homeostasis model assessment. Asian Indians had higher insulin resistance than Chinese or Malays. Impaired glucose tolerance (IGT) and diabetes mellitus (DM) were associated with greater insulin resistance and impaired beta-cell function compared to normal glucose tolerance (NGT). Insulin resistance was positively correlated with blood pressure in women and total cholesterol, LDL cholesterol and triglyceride in both men and women. It was negatively correlated with HDL cholesterol and LDL/apolipoprotein B ratio. beta-cell function showed no significant correlations with the cardiovascular risk factors studied. It appears that both impaired beta-cell function and insulin resistance are important for the development of hyperglycemia whereas insulin resistance alone seems more important in the development of coronary artery disease as it correlates with several known coronary artery disease risk factors.
Diabetes mellitus abolishes ethnic differences in cardiovascular risk factors: lessons from a multi-ethnic population

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.
Associations of diabetes mellitus and ethnicity with mortality in a multiethnic Asian population: data from the 1992 Singapore National Health Survey

Ma S, Cutter J, Tan CE, Chew SK, Tai ES

Am J Epidemiol, 2003 Sep 15;158(6):543-52.
PMID: 12965880 DOI: 10.1093/aje/kwg199

Despite the high prevalence of diabetes mellitus, little is known about mortality associated with diabetes in Asia. Therefore, the authors followed 3,492 Chinese, Malay, and Asian Indian adults randomly selected from the general population in Singapore. Data on glucose tolerance, demographic characteristics, and other cardiovascular disease risk factors (lipid profile, blood pressure, smoking status, alcohol consumption, and obesity) were obtained in 1992. Vital status was determined as of December 31, 2001. There were 108 deaths over a period of 9 years. Impaired fasting glycemia or impaired glucose tolerance (IFG/IGT) (hazard ratio (HR)=1.39, 95% confidence interval (CI): 0.84, 2.31) and diabetes mellitus (HR=2.49, 95% CI: 1.58, 3.94) were associated with increased mortality after adjustment for age, gender, ethnic group, and educational level. Compared with Chinese with diabetes, Indians with diabetes experienced significantly greater mortality (HR=3.86, 95% CI: 1.76, 8.44) after adjustment for gender, age, educational level, smoking, hypertension, alcohol intake, and obesity. Undiagnosed diabetes and IFG/IGT were more common than known diabetes and also were associated with increased mortality. For reduction of mortality associated with IFG/IGT and diabetes, the authors recommend a screening program to detect undiagnosed diabetes and IFG/IGT along with aggressive treatment of diabetes after diagnosis.
APOE polymorphism and lipid profile in three ethnic groups in the Singapore population

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.
Dietary fat interacts with the -514C>T polymorphism in the hepatic lipase gene promoter on plasma lipid profiles in a multiethnic Asian population: the 1998 Singapore National Health Survey

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%.
Fulltext Do Singapore patients require lower doses of statins? The SGH Lipid Clinic experience

Tan CE, Loh LM, Tai ES

Singapore Med J, 2003 Dec;44(12):635-8.
PMID: 14770258

A substantial number of physicians in Asian countries believe that Asian patients need lower doses of statins to achieve therapeutic lipid target because of the smaller size of patients. This belief is deep rooted and we looked at the SGH Lipid Clinic to determine if our experience bears out this belief. Between 1996 and August 2000, the Lipid Unit treated a total of 841 patients, of which 548 patients (77.5% Chinese, 12.1% Malays, 7.6% Asian Indians; 49.6% males, 50.4% females; 54.7% diabetics, 45.3% non-diabetic) were on statins alone. These patients had > or =2 coronary risk factors, diabetes mellitus or documented coronary heart disease. The pre-treatment lipid levels or the worst lipid levels available were entered as the baseline lipid values (mean LDL-C: 5.38+1.5 mmol/l). Duration of therapy ranged from six months to five years. The choice and titration of statins were determined by attending physicians. The median statin dose (Simvastatin equivalent) was 20.0 mg with 52.5% requiring 20 mg or more. Statin dose did not differ between diabetic and non-diabetic subjects. The median statin dose was 15 mg for the lower two tertiles and 20 mg for the upper tertile; this difference did not achieve statistical significance. The reduction in LDL cholesterol was 41.5% (40.1-42.8) and total cholesterol was 33.0% (32.9-34.1). Only 25% of our patients achieved LDL cholesterol of less than 2.6 mmol/l whilst 77.5% had LDL cholesterol less than 3.4 mmol/l. Our experience at the Lipid Clinic suggests that the Asian patients require similar statin doses to achieve target cholesterol levels.
The metabolic syndrome in Chinese, Malays and Asian Indians. Factor analysis of data from the 1998 Singapore National Health Survey

Ang LW, Ma S, Cutter J, Chew SK, Tan CE, Tai ES

Diabetes Res Clin Pract, 2005 Jan;67(1):53-62.
PMID: 15620434 DOI: 10.1016/j.diabres.2004.05.003

We used factor analysis to define and compare the manner in which the various features of the metabolic syndrome are linked or clustered in Chinese, Malays and Asian Indians. One thousand nine hundred and fifty seven men (1324 Chinese, 391 Malays and 261 Asian Indians) and 2308 women (1622 Chinese, 391 Malays and 296 Asian Indians) were examined. Anthropometry, blood pressure, serum glucose, lipid concentrations, and serum insulin were measured for all subjects. These data were then subjected to factor analysis which reduced the variables examined to three factors in all ethnic groups and both genders. The first (dyslipidemia) factor was positively loaded for obesity, insulin resistance (IR), fasting triglyceride and negatively loaded for HDL-cholesterol. The second (hyperglycemia) factor was positively loaded for IR and blood glucose. The third (hypertension) factor was positively loaded for obesity and blood pressure. IR was positively loaded in the hypertension factor in Malay women but not in others. Rather than a single entity causally associated with insulin resistance (IR), our findings support a concept in which the metabolic syndrome represents several distinct entities (dyslipidemia, hypertension and hyperglycemia). It appears that Malay females may be more prone to develop hypertension in association with IR.
Intragenic linkage disequilibrium structure of the human perilipin gene (PLIN) and haplotype association with increased obesity risk in a multiethnic Asian population

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.
Uncoupling protein 2 promoter polymorphism -866G/A, central adiposity, and metabolic syndrome in Asians

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.
Ethnicity modifies the association between diabetes mellitus and ischaemic heart disease in Chinese, Malays and Asian Indians living in Singapore

Yeo KK, Tai BC, Heng D, Lee JM, Ma S, Hughes K, et al.

Diabetologia, 2006 Dec;49(12):2866-73.
PMID: 17021918 DOI: 10.1007/s00125-006-0469-z

AIMS/HYPOTHESIS: The aim of the study was to determine whether the risk of ischaemic heart disease (IHD) associated with diabetes mellitus differs between ethnic groups.

METHODS: Registry linkage was used to identify IHD events in 5707 Chinese, Malay and Asian Indian participants from three cross-sectional studies conducted in Singapore between the years 1984 and 1995. The study provided a median of 10.2 years of follow-up with 240 IHD events experienced. We assessed the interaction between diabetes mellitus and ethnicity in relation to the risk of IHD events using Cox proportional hazards regression.

RESULTS: Diabetes mellitus was more common in Asian Indians. Furthermore, diabetes mellitus was associated with a greater risk of IHD in Asian Indians. The hazard ratio when comparing diabetes mellitus with non-diabetes mellitus was 6.41 (95% CI 5.77-7.12) in Asian Indians and 3.07 (95% CI 1.86-5.06) in Chinese (p = 0.009 for interaction). Differences in the levels of established IHD risk factors among diabetics from the three ethnic groups did not appear to explain the differences in IHD risk.

CONCLUSIONS/INTERPRETATION: Asian Indians are more susceptible to the development of diabetes mellitus than Chinese and Malays. When Asian Indians do develop diabetes mellitus, the risk of IHD is higher than for Chinese and Malays. Consequently, the prevention of diabetes mellitus amongst this ethnic group is particularly important for the prevention of IHD in Asia, especially given the size of the population at risk. Elucidation of the reasons for these ethnic differences may help us understand the pathogenesis of IHD in those with diabetes mellitus.
Rationale and methodology for a population-based study of eye diseases in Malay people: The Singapore Malay eye study (SiMES)

Foong AW, Saw SM, Loo JL, Shen S, Loon SC, Rosman M, et al.

Ophthalmic Epidemiol, 2007 Jan-Feb;14(1):25-35.
PMID: 17365815

Although there are approximately 200 million people of Malay ethnicity living in Asia, the burden and risk factors of blinding eye diseases in this ethnic group are unknown. This study summarizes the rationale and study design of a population-based study of eye diseases among adult Malays in Singapore.
Retinal vascular caliber, blood pressure, and cardiovascular risk factors in an Asian population: the Singapore Malay Eye Study

Sun C, Liew G, Wang JJ, Mitchell P, Saw SM, Aung T, et al.

Invest Ophthalmol Vis Sci, 2008 May;49(5):1784-90.
PMID: 18436813 DOI: 10.1167/iovs.07-1450

To describe the relationship of retinal vascular caliber with cardiovascular risk factors in an Asian population.
Hypertension, concurrent cardiovascular risk factors and mortality: the Singapore Cardiovascular Cohort Study

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.
Fulltext Polymorphisms at newly identified lipid-associated loci are associated with blood lipids and cardiovascular disease in an Asian Malay population

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.
Effect of blood pressure on the retinal vasculature in a multi-ethnic Asian population

Jeganathan VS, Sabanayagam C, Tai ES, Lee J, Sun C, Kawasaki R, et al.

Hypertens Res, 2009 Nov;32(11):975-82.
PMID: 19713968 DOI: 10.1038/hr.2009.130

Blood pressure has a significant effect on retinal arterioles. There are few data on whether this effect varies by race/ethnicity. We examined the relationship of blood pressure and retinal vascular caliber in a multi-ethnic Asian population. The study is population-based and cross sectional in design. A total of 3749 Chinese, Malay and Indian participants aged > or =24 years residing in Singapore were included in the study. Retinal vascular caliber was measured using a computer program from digital retinal photographs. The associations of retinal vascular caliber with blood pressure and hypertension in each racial/ethnic group were analyzed. The main outcome measures are retinal arteriolar caliber and venular caliber. The results show that retinal arterioles were narrower in persons with uncontrolled/untreated hypertension (140.0 microm) as compared with persons with controlled hypertension (142.1 microm, P=0.0001) and those with no hypertension (146.0 microm, P<0.0001). On controlling for age, gender, body mass index, lipids and smoking, each 10 mm Hg increase in mean arterial blood pressure was associated with a 3.1 microm decrease in arteriolar caliber (P<0.0001), with a similar magnitude seen in all three racial/ethnic groups: 3.1 microm in Chinese, 2.8 microm in Malays and 3.2 microm in Indians (P<0.0001 for all). Each 10 mm Hg increase in mean arterial blood pressure was associated with a 1.8 microm increase in venular caliber (P<0.0001); furthermore, the magnitude of this effect was similar across the three racial/ethnic groups. The effect of blood pressure on the retinal vasculature was similar across three major racial/ethnic groups in Asia.
Polymorphisms identified through genome-wide association studies and their associations with type 2 diabetes in Chinese, Malays, and Asian-Indians in Singapore

Tan JT, Ng DP, Nurbaya S, Ye S, Lim XL, Leong H, et al.

J Clin Endocrinol Metab, 2010 Jan;95(1):390-7.
PMID: 19892838 DOI: 10.1210/jc.2009-0688

CONTEXT:
Novel type 2 diabetes mellitus (T2DM) susceptibility loci, identified through genome-wide association studies (GWAS), have been replicated in many European and Japanese populations. However, the association in other East Asian populations is less well characterized.

OBJECTIVE:
To examine the effects of SNPs in CDKAL1, CDKN2A/B, IGF2BP2, HHEX, SLC30A8, PKN2, LOC387761, and KCNQ1 on risk of T2DM in Chinese, Malays, and Asian-Indians in Singapore.

DESIGN:
We genotyped these candidate single-nucleotide polymorphisms (SNPs) in subjects from three major ethnic groups in Asia, namely, the Chinese (2196 controls and 1541 cases), Malays (2257 controls and 1076 cases), and Asian-Indians (364 controls and 246 cases). We also performed a metaanalysis of our results with published studies in East Asians.

RESULTS:
In Chinese, SNPs in CDKAL1 [odds ratio (OR) = 1.19; P = 2 x 10(-4)], HHEX (OR = 1.15; P = 0.013), and KCNQ1 (OR = 1.21; P = 3 x 10(-4)) were significantly associated with T2DM. Among Malays, SNPs in CDKN2A/B (OR = 1.22; P = 3.7 x 10(-4)), HHEX (OR = 1.12; P = 0.044), SLC30A8 (OR = 1.12; P = 0.037), and KCNQ1 (OR = 1.19-1.25; P = 0.003-2.5 x 10(-4)) showed significant association with T2DM. The combined analysis of the three ethnic groups revealed significant associations between SNPs in CDKAL1 (OR = 1.13; P = 3 x 10(-4)), CDKN2A/B (OR = 1.16; P = 9 x 10(-5)), HHEX (OR = 1.14; P = 6 x 10(-4)), and KCNQ1 (OR = 1.16-1.20; P = 3 x 10(-4) to 3 x 10(-6)) with T2DM. SLC30A8 (OR = 1.06; P = 0.039) showed association only after adjustment for gender and body mass index. Metaanalysis with data from other East Asian populations showed similar effect sizes to those observed in populations of European ancestry.

CONCLUSIONS:
SNPs at T2DM susceptibility loci identified through GWAS in populations of European ancestry show similar effects in Asian populations. Failure to detect these effects across different populations may be due to issues of power owing to limited sample size, lower minor allele frequency, or differences in genetic effect sizes.
Fulltext Ethnic disparities in prevalence and impact of risk factors of chronic kidney disease

Sabanayagam C, Lim SC, Wong TY, Lee J, Shankar A, Tai ES

Nephrol Dial Transplant, 2010 Aug;25(8):2564-70.
PMID: 20185856 DOI: 10.1093/ndt/gfq084

There is substantial heterogeneity in literature regarding the epidemiology for chronic kidney disease (CKD) in different Asian populations. We aimed to assess the prevalence and risk factors of CKD in a multi-ethnic Asian population in Singapore.
Fulltext Collagen-related genes influence the glaucoma risk factor, central corneal thickness

Vithana EN, Aung T, Khor CC, Cornes BK, Tay WT, Sim X, et al.

Hum Mol Genet, 2011 Feb 15;20(4):649-58.
PMID: 21098505 DOI: 10.1093/hmg/ddq511

Central corneal thickness (CCT) is a risk factor of glaucoma, the most common cause of irreversible blindness worldwide. The identification of genetic determinants affecting CCT in the normal population will provide insights into the mechanisms underlying the association between CCT and glaucoma, as well as the pathogenesis of glaucoma itself. We conducted two genome-wide association studies for CCT in 5080 individuals drawn from two ethnic populations in Singapore (2538 Indian and 2542 Malays) and identified novel genetic loci significantly associated with CCT (COL8A2 rs96067, p(meta) = 5.40 × 10⁻¹³, interval of RXRA-COL5A1 rs1536478, p(meta) = 3.05 × 10⁻⁹). We confirmed the involvement of a previously reported gene for CCT and brittle cornea syndrome (ZNF469) [rs9938149 (p(meta) = 1.63 × 10⁻¹⁶) and rs12447690 (p(meta) = 1.92 × 10⁻¹⁴)]. Evidence of association exceeding the formal threshold for genome-wide significance was observed at rs7044529, an SNP located within COL5A1 when data from this study (n = 5080, P = 0.0012) were considered together with all published data (reflecting an additional 7349 individuals, p(Fisher) = 1.5 × 10⁻⁹). These findings implicate the involvement of collagen genes influencing CCT and thus, possibly the pathogenesis of glaucoma.
Hypertension, hypertension control, and chronic kidney disease in a Malay population in Singapore

Sabanayagam C, Shankar A, Lim SC, Tai ES, Wong TY

Asia Pac J Public Health, 2011 Nov;23(6):936-45.
PMID: 20460283 DOI: 10.1177/1010539510361637

Studies conducted in Western populations demonstrate that blood pressure (BP) is a major risk factor for chronic kidney disease (CKD). The authors examined the cross-sectional association between BP and CKD in 3280 adults of Malay ethnicity aged 40 to 80 years living in Singapore. CKD was defined as (1) estimated glomerular filtration rate (eGFR) of < 60 mL/min/1.73 m(2) and (2) presence of microalbuminuria/macroalbuminuria. They observed a dose-dependent positive association between BP and CKD (P trend < .0001). In multivariable-adjusted analysis, compared with participants with normal BP, the odds ratio (OR; 95% confidence interval [CI]) of eGFR < 60 mL/min/1.73 m(2) was 1.85 (0.95-3.62), 2.95 (1.55-5.64), and 4.96 (2.63-9.37) for prehypertension, and stage 1 and stage 2 hypertension, respectively. Similar results were obtained for microalbuminuria/macroalbuminuria. Stage 2 hypertension had the greatest population-attributable risk of CKD (23%). The strong positive association of hypertension with CKD emphasizes the need to control BP in Asian populations to reduce the burden of kidney disease.
Fulltext Rapid detection of pathogenic leptospires by lyophilized reagent-based polymerase chain reaction

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.

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