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.
AIM: The purpose of this study is to compare the prevalence of rheumatoid factor (RF) isotypes and second generation anti-cyclic citrullinated peptides (anti-CCP) in Malaysian rheumatoid arthritis (RA) patients.
METHODS: In this cross-sectional study, 147 established RA patients from three ethnic groups were recruited from a major rheumatology clinic in Malaysia. Enzyme-linked immunosorbent assays (ELISA) for serum RF isotypes IgA, IgG and IgM as well as second-generation anti-CCP were performed and the prevalence of each auto-antibody was compared in the three ethnic groups.
RESULTS: The anti-CCP was the most prevalent auto-antibody in each of the ethnic groups, followed closely by RF IgM and RF IgG. Rheumatoid factor IgA was the least prevalent across all three ethnic groups. The anti-CCP-RF IgM combination provided the best test sensitivity. Seroprevalence of anti-CCP was strongly associated with the presence of each of the RF isotypes. The seroprevalence of RF and anti-CCP did not increase or decrease with advancing age, age at onset and disease duration.
CONCLUSION: When used alone, anti-CCP provides a diagnostic advantage over RF IgM on the basis of test sensitivity. Considering the high cost of the anti-CCP assay, step-wise serum testing with IgM RF followed by anti-CCP may provide a more economically sensible option to optimize test sensitivity for RA.
Study site: Rheumatology clinic, Hospital Tuanku Jaafar, Seremban, Negeri Sembilan, Malaysia
INTRODUCTION: Female sexual dysfunction (FSD) is a highly prevalent sexual health problem but poorly investigated at the primary care level.
AIM: This article examines the prevalence of sexual dysfunction and its possible risk factors associated with women at high risk of FSD in a hospital-based primary practice.
METHODS: A validated Malay version of the Female Sexual Function Index (MVFSFI) was utilized to determine FSD in a cross-sectional study design, involving 163 married women, aged 18-65 years, in a tertiary hospital-based primary care clinic in Kuala Lumpur, Malaysia. Sociodemographic, marital profile, health, and lifestyle for women at high risk of FSD and those who were not at high risk were compared and their risk factors were determined.
MAIN OUTCOME MEASURES: Prevalence of FSD in Malaysian women based on the MVFSFI, and its risk factors for developing FSD.
RESULTS: Some 42 (25.8%) out of 163 women had sexual dysfunction. Prevalence of sexual dysfunction increased significantly with age. Sexual dysfunctions were detected as desire problem (39.3%), arousal problem (25.8%), lubrication problem (21.5%), orgasm problem (16.6%), satisfaction problem (21.5%) and pain problems (16.6%). Women at high risk of FSD were significantly associated with age (OR 4.1, 95% CI 1.9 to 9.0), husband's age (OR 4.3 95% C.I 1.9 to 9.3), duration of marriage (OR 3.3, 95% CI 1.6 to 6.8), medical problems (OR 8.5, 95% CI 3.3 to 21.7), menopausal status (OR 6.6, 95% CI 3.1 to 14.3), and frequency of sexual intercourse (OR 10.7, 95% CI 3.6 to 31.7). Multivariate analysis showed that medical problem (adjusted OR 4.6, 95% CI 1.6 to 14.0) and frequency of sexual intercourse (adjusted OR 7.2, 95% CI 2.1 to 24.0) were associated with increased risk of having FSD. Those who practiced contraception were less likely to have FSD.
CONCLUSION: Sexual health problems are prevalent in women attending primary care clinic where one in four women were at high risk of FSD. Thus, primary care physician should be trained and prepared to address this issue.
Study site: Primary Care Clinic, University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia
The frequencies of alleles implicated in drug-response variability provide vital information for public health management. Differences in frequencies between genetically diverse groups of individuals can hamper drug assessments, particularly in populations where clinical data are not readily available.
BACKGROUND: Managed care is one of the means advocated for health care reforms. The Malaysian government has proposed managed care for its citizens. In the Malaysian private health care sector, managed care is practised on a small scale with crude risk adjustment. The main determinant of an individual's health service utilization is their health status (HS). HS is used as a risk adjuster for capitation payment. Prescribed medications represent a useful source for HS estimation. We aimed to develop and validate a medication-based HS estimate and to incorporate it in the Andersen model of health service utilization. This is a preparatory step in studying the feasibility of developing a model for risk assessment in the Malaysian context.
METHODS: Data were collected retrospectively from an academic year from computerized databases in University Sains Malaysia (USM) about users of USM primary care services. A user is a USM health scheme beneficiary who made at least one visit in the academic year to USM-assigned primary care providers. Socio-demographic variables, enrolment period, medications prescribed and number of visits were also collected. Chronic illness medications and some non-chronic illness medications were used to calculate the Long-Term Therapeutic Groups Index (LTTGI) which is an estimate of the HS of users. Using a random 50% of users, weighted least square methods were used to develop a model that predicts a user's number of visits. The other 50% were used for validation.
RESULTS: Socio-demographic variables explained 15% of variability in number of primary care visits among users. Adding the LTTGI improved the explanatory power of the model to 36% (P < 0.001). A similar contribution of the LTTGI was noted in the validation.
CONCLUSIONS: The Long-Term Therapeutic Groups Index was successfully developed. Variability in number of primary care visits can be predicted by LTTGI-based models.
Increased total homocysteine (tHcy) is a risk factor for stroke. This study examines whether the efficacy of B-vitamins in reducing tHcy is modified by ethnicity in a Singaporean ischemic stroke population.
Many studies in Asia have demonstrated that Asian populations may require lower cut-off levels for body mass index (BMI) and waist circumference to define obesity and abdominal obesity respectively, compared to western populations. Optimal cut-off levels for body mass index and waist circumference were determined to assess the relationship between the two anthropometric- and cardiovascular indices. Receiver operating characteristics analysis was used to determine the optimal cut-off levels. The study sample included 1833 subjects (mean age of 44+/-14 years) from 93 primary care clinics in Malaysia. Eight hundred and seventy two of the subjects were men and 960 were women. The optimal body mass index cut-off values predicting dyslipidaemia, hypertension, diabetes mellitus, or at least one cardiovascular risk factor varied from 23.5 to 25.5 kg/m2 in men and 24.9 to 27.4 kg/m2 in women. As for waist circumference, the optimal cut-off values varied from 83 to 92 cm in men and from 83 to 88 cm in women. The optimal cut-off values from our study showed that body mass index of 23.5 kg/m2 in men and 24.9 kg/m2 in women and waist circumference of 83 cm in men and women may be more suitable for defining the criteria for overweight or obesity among adults in Malaysia. Waist circumference may be a better indicator for the prediction of obesity-related cardiovascular risk factors in men and women compared to BMI. Further investigation using a bigger sample size in Asia needs to be done to confirm our findings.
Study site: 93 primary care clinics (klinik kesihatan and general practice clinics) in Malaysia
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.
OBJECTIVES: To assess the validity, feasibility and acceptability of standard gamble (SG) and time trade-off (TTO) assessments in a multiethnic Asian population.
METHODS: Through in-depth interviews performed among Chinese, Malay, and Indian Singaporeans (education >or= 6 years), we assessed validity of SG/TTO methods for eliciting health preferences by hypothesizing that 1) SG/TTO scores for three hypothetical health states (HS) would exhibit ranked order (decreasing scores with worse HS); and 2) more subjects would rate the most severe HS as worse than dead. Subjects also evaluated feasibility and acceptability of SG/TTO using a 10-point visual analog scale (VAS) and open-ended questions. Ratings were compared using Kruskal-Wallis, Wilcoxon signed-rank tests or tests of proportions.
RESULTS: VALIDITY: In 62 subjects (90% response rate), as hypothesized, SG and TTO scores exhibited ranked order with increasing HS severity (SG: 0.85, 0.08, -19.00; TTO: 0.85, 0.00, -0.18). More subjects rated the most severe HS as worse than dead (SG: 8%, 39%, 59%; TTO: 8%, 45% and 62%).
FEASIBILITY: Subjects felt SG and TTO were easy to understand (median VAS scores: 8.0 vs. 8.0, P = 0.87) and to complete (8.0 vs. 8.0, P = 0.84). Acceptability: SG and TTO were well accepted, with TTO less so than SG (median [interquartile range] offensiveness: 2.0 [0, 4.0] vs. 2.0 [0, 3.0], P = 0.045). Overall, subjects did not have a clear preference for SG/TTO (50% vs. 45%, P = 0.70).
CONCLUSIONS: This study suggests the validity, feasibility and acceptability of SG and TTO for population-based HS valuation studies in a multiethnic Asian population.
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.
This study aimed to determine the prevalence and pattern of insomnia in a Malaysian population aged 30 to 70 years. The sample consisted of 1611 subjects, recruited by stratified random sampling and interviewed using a semistructured questionnaire conducted in 2004. This was a community-based survey in 4 Malaysian states. The prevalence of insomnia symptom was 33.8%, and 12.2% of the subjects had chronic insomnia. Insomnia was more common among elderly; those who were separated, divorced, or widowed; and those who smoked at bedtime. Subjects with insomnia had a higher prevalence of feeling depressed (12.7), loss of concentration (19.1%), exhaustion (17.2%), poor memory (9.2%), decreased work productivity (6.4%), and perceived poor health status (40.9%; all, P < .05). A total of 22.2% of those with insomnia had excessive daytime sleepiness based on their Epworth Sleepiness Score (P =
INTRODUCTION: routine rubella antibody screening is not done for antenatal mothers in community health clinics in Malaysia. However, congenital rubella syndrome has persisted with its associated health burden.
OBJECTIVES: to determine the prevalence of rubella susceptibility among pregnant mothers and its associated risk factors.
METHODOLOGY: a cross-sectional study was carried out in the Petaling district, Selangor, Malaysia, where 500 pregnant mothers were recruited, and face-to-face interviews were conducted. Rubella IgG tests were performed.
RESULTS: the prevalence of rubella susceptibility among pregnant mothers was 11.4%. Using logistic regression, a history of not having received rubella vaccination or having unknown rubella vaccination status was found to be a significant predictor for mothers to be rubella susceptible (odds ratio = 2.691; 95% confidence interval = 1.539-4.207).
CONCLUSIONS: routine rubella IgG screening tests need to be offered to all antenatal mothers in view of the high prevalence found.
Study site: Antenatal clinics (klinik kesihatan), Petaling, Selangor, Malaysia
To determine the prevalence, distribution, severity and treatment need of enamel opacities among 11-12 year-old school children in a fluoridated urban community.
Organophosphate (OP)-containing pesticides are widely used worldwide for domestic and industrial purposes. Studies on acute and chronic exposure to OPs have revealed numerous health effects attributed mainly to acetylcholinesterase (AChE) inhibition. The enzyme human serum paraoxonase (PON1) is involved in the detoxification of OP compounds. PON1 polymorphisms have been shown to affect susceptibility to OP exposure. We studied the effect of OP exposure on pest control workers and assessed the distribution of two common PON1 polymorphisms in our local population. The exposed group consisted of 103 workers from various pest control companies under the Singapore Pest Management Association while the 91 unexposed workers were from a lead stabilizer factory. For all workers, the mean age was 36.9 (20-70) years and the ethnic distribution was 38.1% Chinese, 44.3% Malay and 17.5% Indian. The mean+/-S.D. exposure duration among the pesticide workers was 10.4+/-8.4 years. The mean+/-S.D. RBC cholinesterase level was 18436.2+/-2078U/L and 18079.6+/-1576U/L for the exposed and unexposed groups, respectively (p=0.216). The mean+/-S.D. serum pseudocholinesterase was 11028.4+/-2867.4U/L and 9433.6+/-2022.6U/L in the exposed and unexposed groups, respectively (p<0.0001). Mean paraoxonase activity was similar among Chinese and Malays (266.5 and 266.3U/L, respectively) whereas that of the Indians was significantly lower (165.6U/L). Our study showed that cholinesterase levels among the exposed were not lower than those in the unexposed group. PON1 polymorphisms differed among ethnic groups, implying that ethnicity could be an important surrogate for identifying susceptible groups in case of OP exposure. Although OP poisoning is rare among occupationally exposed workers in Singapore, this information is useful for other developing countries that have large populations of Chinese, Malays and Indians where OP exposure could be very high especially in agricultural settings.
Motorcycle casualties represent significant number in road traffic accidents in Malaysia, and among all the injuries, facial injuries pose many significant problems physiologically, functionally, and aesthetically. The aim of this study was to analyze the pattern of maxillofacial as well as other injuries in motorcyclists who were seen at Hospital Universiti Kebangsaan Malaysia.Patients' records from January 2004 to December 2005 were reviewed. Data related to demographics, vehicle/object involved in collision, involvement as a rider or pillion, whether a helmet was worn or not, location of injuries on the face/facial bones, and other associated injuries were collected.A total of 113 cases of motorcycle accidents were recorded; 106 males and 7 females were involved. Mean age was 25.8 years. Among all the races, Malay had the highest involvement (72.3%), followed by Chinese (14.3%), Indians (8.9%), and others (5.4%). The types of collision were either a single-vehicle collision (i.e., skidded) or with another vehicle/s or object (e.g., tree, stone, or lamppost). The injuries were mainly seen on the lower face (46.9%) followed by midface (25.7%) and a combination of the midface and lower face (15%) and others (12.4%). The most frequent other associated injuries recorded were orthopedic and head injuries.
The prevalence of thyroid-associated ophthalmopathy (TAO) has been reported to be lower in several Asian populations than in Caucasians. The risk factors for TAO that have been demonstrated in Caucasians have not been studied in Asian populations. The aim of this study, therefore, was to determine the prevalence, risk factors, and clinical features of TAO in a cohort of multiethnic Malaysian patients with Graves' disease (GD).
The increasing prevalence of childhood asthma has become a concern among health practitioners. Effective management emphasizes long-term management and inhaled therapy has become the mainstay home management for children. However, proper utilization of medication is pertinent in improving control. Proper asthma education is mandatory in improving skills and confidence amongst parents. To assess the skills of using the metered-dose inhaler (MDI) with a spacer among asthmatic children before and after educational intervention and to analyse any difficulties which may occur amongst the participants in executing the assessment steps. A cross-sectional clinic based study involving 85 parents and children with asthma. A standardized metered-dose inhaler-spacer checklist of eight steps of medication usage and five steps of cleaning the spacer were used as the assessment tools for pre and post intervention. The performance on using the inhaler-spacer and spacer cleaning knowledge pre and two months post intervention was evaluated. One point was given for each correct step and zero points for incorrect answers/steps. The mean score for skills of inhaler technique improved significantly after educational intervention (3.51 to 6.01, p < 0.0001) as did the mean score for parental knowledge of spacer cleaning technique (1.35 to 3.16, p 0.001). Analysis showed only a limited improvement even after an educational session in three steps of inhalation technique: step 5 (23.5%/69.4%), step 6 (28.2%/68.2%) and step 7 (25.9%/61.2%). Parents with asthmatic children had poor skills in utilizing their children's medication. A short-term educational intervention was able to improve overall knowledge and skill but certain skills need more emphasizing and training.
Study site: Klink HUKM Taman Jaya, Cheras, Kuala Lumpur, Malaysia (primary care clinic for Hospital University Kebangsaan Malaysia)
Anemia is the most prevalent nutritional deficiency during pregnancy. Except for a study conducted 10 years ago in Kelantan, Malaysia's available statistics are based on isolated small urban maternity hospital studies from the 1980s. There was therefore, a need for a large study at national level to estimate the magnitude of the problem in the country as well as to understand its epidemiology. This multi-center, cross-sectional study was conducted from February to March 2005, to assess the prevalence of anemia. Multistage stratified random sampling technique was used and 59 Ministry of Health (MOH) primary health care clinics were selected. Our final dataset consisted of 1,072 antenatal mothers from 56 clinics. The overall prevalence of anemia in this population was 35 % (SE 0.02) if the cut off level is 11 g/dL and 11 % (SE 0.03) if the cut-off level is 10 g/dL. The majority was of the mild type. The prevalence was higher in the teenage group, Indians followed by Malays and Chinese being the least, grandmultiparas, the third trimester and from urban residence. After multiple linear regression analysis, only gestational age remained significant. These findings are useful for our Maternal Health program planners and implementers to target and evaluate interventions. Work is in progress for outcomes and cost-effectiveness studies to best tackle this problem. In conclusion, the prevalence of anemia is 35% and mostly of the mild type and more prevalent in the Indian and Malays.
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.