Multiethnic Malaysian Population Research Articles

Association Analysis of a GSTP1 Functional Polymorphism with Methamphetamine Dependence and Associated Symptoms in a Multiethnic Malaysian Population

Methamphetamine (METH) is a psychostimulant that is highly addictive and has been widely linked to the adverse effect on brain. METH-induced oxidative stress can be effectively protected by glutathione S-transferases (GSTs). Genetic polymorphism of GST gene family may affect the susceptibility of METH users to its dependence and associated symptoms. Therefore, this study investigated the association of a functional single nucleotide polymorphism rs1695 of GSTP1 gene with METH-induced symptoms and dependence in a Malaysian population, including Malay, Chinese, Kadazan-Dusun, and Bajau ethnic groups. Genotyping for GSTP1 rs1695 polymorphism from 230 METH-dependent male subjects and 232 healthy male controls was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RLFP). For statistical analyses, the χ2 test and Fisher’s were performed in this research. The results showed a significant difference between GSTP1 rs1695 polymorphism and METH dependence in the Malay and Chinese populations. Our findings suggest that the GSTP1 rs1695 polymorphism may have possibility to methamphetamine dependence in the Malay and Chinese populations but not in other ethnicities. Furthermore, the Malay ethnic group who carried the -105G allele might have a protective role for METH-induced mania.

Esophageal squamous cell carcinoma and adenocarcinoma in Malaysia – Pooled data from upper gastrointestinal centers in a multiethnic Asian population

BackgroundEsophageal cancer is the sixth leading cause of cancer death worldwide with considerable geographical histological variation There is a paucity of data in esophageal cancer in demographics, histology, and survival among the multi-ethnic Malaysian population. This paper is a review of esophageal cancer epidemiology and survival among esophageal cancer patients from data collected by the Malaysian Upper Gastrointestinal Surgical Society. MethodsThis is a multicenter retrospective observational study of esophageal cancer patients from six upper gastrointestinal surgical centers in Malaysia between 2005 and 2019. Patient characteristics, histological type and stage were compared and survival analyzed. ResultsThere were 820 patients with esophageal cancer included, where 442 (53.9 %) cases had squamous cell carcinoma (SCC) and 378 (46.1 %) had adenocarcinomas (AC). Malays were the predominant ethnicity with AC (66.7 %) while Indians were the ethnic majority (74.6 %) with SCC. Majority of patients (56.8 %) presented as stage IV disease. Overall, the 1-, 3-, and 5-years’ survival were 35.8 %, 13.8 % and 11.0 %, respectively. Surgical resection with curative intent yielded the best 5-year survival (29.4 %). Intervention in stage IV AC yielded superior survival when compared to SCC (median survival, 7.9 months vs 4.8 months; p, 0.018) Our series demonstrated an increase in AC to SCC over the last 15 years. ConclusionsThere was an ethnic preponderance seen between different histology in this region, not previously discussed. An increase in AC was observed over the last 15 years. Late diagnosis seen in most patients imparts poor prognosis as curative surgery affords the best outcome.

Characterization of Multiple Omics Signatures in Relation to Dietary Pattern for in Silico Personalised Colon Cancer Risk Stratification: Study Protocol for a Case-control Study and the Challenges Faced During the COVID-19 Pandemic

Background: Personalised nutrition and medicine are the future of healthcare. In relation to cancer, public and healthcare professionals often seek dietary recommendations for cancer prevention. Among the important cancers that can be prevented by diet and lifestyle is colorectal cancer (CRC). CRC is one of the commonest cancers globally, and is a major health concern in Malaysia as it presents with high mortality and morbidity rates, causing a significant socioeconomic burden to the country. While extensive research has been conducted on the treatment and mechanisms of cancer, there have been no reports on the associations between metabolites, novel biomarkers of cancer, and dietary patterns in the context of cancer prevention in the Malaysian multiethnic population. Methods: A case control study will be conducted in Malaysia, involving patients diagnosed with CRC, colorectal adenoma and a group of healthy participants. Multiple endpoints will be analyzed, namely metabolomic signatures, epigenetic marks, inflammatory markers and relationship with dietary patterns will be established. Multiple machine learning models will then be used to develop personalised risk stratification algorithms. Recruitment began in July 2019 and is ongoing due to COVID-19 pandemic. Discussion: This study will be the first to identify alterations in metabolites, inflammatory markers and epigenetic marks associated with dietary patterns and CRC risk in Malaysia. Understanding on how dietary patterns influence CRC risk in the multi-ethnic Malaysian population and identification of novel oncometabolites for CRC risk, will allow for development of personalised evidence-based recommendations in reducing individual risks of CRC.

Management of gout in the primary care setting.

Gout is a commonly treated inflammatory arthritis that is often managed in the primary care setting. This disease is prevalent among the multi-ethnic Malaysian population. Unfortunately, gout is still frequently managed sub-optimally, even in the hospital and primary care settings. Gout should be considered a major disease since it can potentially lead to multiple disabilities from joint destruction, nephropathy and increased cardiovascular morbidity and mortality. The objectives of this review are to summarise the latest updated information and management of gout in the primary care setting.

Hereditary transthyretin amyloidosis in multi-ethnic Malaysians

We report the clinical and genetic characteristics of hereditary transthyretin amyloidosis in the multi-ethnic Malaysian population. Subjects with genetically confirmed transthyretin amyloidosis seen between 2001 till August 2020 were included. There were 30 patients and 14 asymptomatic carriers, of which 26 (59.1%) were men. The majority (86.7%) were ethnic Chinese while two (6.7%) each were Malay and Sri Lankan Tamil ethnicity respectively. Among patients, mean age of symptom-onset was 55.9 ± 9.8 years with mean duration from symptom-onset to diagnosis of 3.2 ± 2.5 years. Common presenting symptoms were sensory symptoms of upper limbs (43.3%), symmetric sensory symptoms of both lower limbs (16.7%) and autonomic symptoms (16.7%). Nerve conduction studies showed sensorimotor polyneuropathy in 25 (83.3%) patients (22, axonal). Abnormal echocardiograms were seen in 24 (80%) patients, although 15 were asymptomatic. Of six different TTR mutations found, Ala97Ser was the commonest, and found exclusively in 84.6% of Chinese patients. Other mutations among Chinese patients were Val30Met, Ala25Thr and Asp39Val. Our Malay and Tamil patients had Glu54Lys and Gly47Val mutations respectively. In conclusion, TTR Ala97Ser is the commonest mutation among ethnic Chinese Malaysians which presented with late-onset progressive sensorimotor polyneuropathy, autonomic dysfunction and subclinical cardiac involvement.

The spectrum of association in HLA region with rheumatoid arthritis in a diverse Asian population: evidence from the MyEIRA case-control study

BackgroundFine-mapping of human leukocyte antigen (HLA) region for rheumatoid arthritis (RA) risk factors has identified several HLA alleles and its corresponding amino acid residues as independent signals (i.e., HLA-A, HLA-B, HLA-DPB1, and HLA-DQA1 genes), in addition to the well-established genetic factor in HLA-DRB1 gene. However, this was mainly performed in the Caucasian and East Asian populations, and data from different Asian regions is less represented. We aimed to evaluate whether there are independent RA risk variants in both anti-citrullinated protein antibody (ACPA)-positive and ACPA-negative RA patients from the multi-ethnic Malaysian population, using the fine-mapping of HLA region strategy.MethodsWe imputed the classical HLA alleles, amino acids, and haplotypes using the Immunochip genotyping data of 1260 RA cases (i.e., 530 Malays, 259 Chinese, 412 Indians, and 59 mixed ethnicities) and 1571 controls (i.e., 981 Malays, 205 Chinese, 297 Indians, and 87 mixed ethnicities) from the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA) population-based case-control study. Stepwise logistic regression was performed to identify the independent genetic risk factors for RA within the HLA region.ResultsWe confirmed that the HLA-DRB1 amino acid at position 11 with valine residue conferred the strongest risk effect for ACPA-positive RA (OR = 4.26, 95% CI = 3.30–5.49, PGWAS = 7.22 × 10−29) in the Malays. Our study also revealed that HLA-DRB1 amino acid at position 96 with histidine residue was negatively associated with the risk of developing ACPA-positive RA in the Indians (OR = 0.48, 95% CI = 0.37–0.62, PGWAS = 2.58 × 10−08). Interestingly, we observed that HLA-DQB1*03:02 allele was inversely related to the risk of developing ACPA-positive RA in the Malays (OR = 0.17, 95% CI = 0.09–0.30, PGWAS = 1.60 × 10−09). No association was observed between the HLA variants and risk of developing ACPA-negative RA in any of the three major ethnic groups in Malaysia.ConclusionsOur results demonstrate that the RA-associated genetic factors in the multi-ethnic Malaysian population are similar to those in the Caucasian population, despite significant differences in the genetic architecture of HLA region across populations. A novel and distinct independent association between the HLA-DQB1*03:02 allele and ACPA-positive RA was observed in the Malays. In common with the Caucasian population, there is little risk from HLA region for ACPA-negative RA.

Influence of Demographic Factors on Nerve Ultrasound of Healthy Participants in a Multiethnic Asian Population.

Background:High-resolution nerve ultrasound provides morphological information of peripheral nerves. We aimed to determine the normal ultrasonographic reference values of nerve cross-sectional area (CSA) in multiethnic Malaysian healthy participants.Methods:Nerve ultrasound of the median, ulnar, radial, tibial, fibular, and sural nerves was performed in 84 healthy participants at anatomical-defined locations. The CSA at each scanned site was measured by tracing circumferentially inside the hyperechoic rim of each nerve. Comparisons were made between genders and ethnic groups. Correlations with age, ethnicity, gender, height, weight, and body mass index (BMI) were evaluated.Results:CSA values and reference ranges in healthy participants were generated. Nerve CSA was significantly different in different gender (P = 0.002–0.032) and ethnic groups (P = 0.006–0.038). Men had larger nerve CSA than women, and Malay participants had larger nerve CSA compared to other ethnic groups. Nerve CSA had significant correlations to age, height, weight, and BMI (r = 0.220–0.349, P = 0.001–0.045).Conclusion:This study provides normative values for CSA of peripheral nerves in a multiethnic Malaysian population, which serves as reference values in the evaluation of peripheral nerve disorders. The ethnic differences in nerve CSA values should be considered during nerve ultrasound.

HLA-B*58: 01 association in allopurinol-induced severe cutaneous adverse reactions: the implication of ethnicity and clinical phenotypes in multiethnic Malaysia.

The association between human leukocyte antigen (HLA)-B*58:01 and risk of allopurinol-induced severe cutaneous adverse reactions (AIS) was observed across different populations. We explore the association between HLA-B*58:01 and AIS risk in multiethnic Malaysian population. The HLA-B*58:01 risk for different AIS clinical phenotypes and ethnicity was determined. We performed a case-control association study by genotyping the HLA-B alleles of 55 patients with AIS [11 toxic epidermal necrolysis (TEN), 21 Steven Johnson syndrome (SJS) 22 drug reaction wit eosinophilia and systemic symptoms (DRESS) and one acute generalized exanthematous pustulosis (AGEP)] and 42 allopurinol-tolerant controls (ATC). HLA-B*58:01 was positive in 89.1 and 14.3% of the AIS and ATC study groups [odds ratio (OR) = 49.0, 95% confidence interval (CI) = 14.6-164.4, P < 0.0001)], respectively. Our data showed that 93.8% of the AIS-SJS/TEN patients and 86.4% of the AIS-DRESS patients were HLA-B*58:01 positive (AIS-SJS/TEN, OR = 90, 95% CI = 16.9-470.1, P < 0.0001 and AIS-DRESS OR = 38, 95% CI = 8.5-169.2, P < 0.0001). Stratification by ethnicity and clinical phenotypes revealed a significant increased risk between HLA-B*58:01 and Chinese-AIS patients (OR = 137.5, 95% CI = 11.3-1680.2, P < 0.0001), in particular Chinese patients with AIS-SJS/TEN phenotype (100% HLA-B*58:01 positive). HLA-B*58:01 was positive in 90.9% Chinese AIS-DRESS (P < 0.0001). Highly significant associations of HLA-B*58:01 were observed in Malay AIS-SJS/TEN (OR = 78, 95% CI = 9.8-619.9, P < 0.0001) and Malay AIS-DRESS (OR = 54, 95% CI = 6.6-442.9, P < 0.0001). Although the number of Indian-AIS patients was relatively small (n = 2), both were HLA-B*58:01 positive. Our data suggest strong associations between HLA-B*58:01 and AIS in Malaysian population with Chinese and Malays ethnicity. The strong association was also observed in three different clinical phenotypes of AIS, mainly the AIS-SJS/TEN.

Therapeutic Plasma Exchange in Neuromyelitis Optica Spectrum Disorders and Related Disorders in Resource-Limited Settings: Outcomes in a Multiethnic Single-Center Population.

We evaluated therapeutic plasma exchange (TPE) efficiency in treatment of a single relapse in steroid-refractory patients with neuromyelitis optica spectrum disorders (NMOSD) in a multi-ethnic resource-limited setting. This was a historical cohort study on the clinical outcomes post-TPE in a multiethnic cohort of 53 steroid-refractory NMOSD patients at a single Malaysian tertiary center. Primary outcomes, assessed both pre- and post-TPE, were Medical Research Council scale of muscle power, Modified Rankin Scale, Expanded Disability Status Scale (EDSS), and visual acuity. Secondary outcomes were ambulatory status and target neurological deficit (TND)-based TPE response. Significant improvements in Medical Research Council, Modified Rankin Scale, EDSS, and visual acuity (P < 0.001) were observed at 1-month post-TPE with further improvement of EDSS at 6 months (EDSSΔ6) post-TPE (P < 0.001). At 6 months post-TPE, 87% of patients has successful TND-based TPE response and 69.8% were ambulating without support. Patients with anti-aquaporin 4 seronegativity (P = 0.004), myelitis and brainstem features at first relapse (P = 0.004), longer cord lesions (P = 0.030), higher pre-TPE EDSS of ≥8 (P = 0.018) and delayed TPE initiation of >14 days (P = 0.047) were significantly associated with improved EDSSΔ6. TND-based TPE response was significant in absence of cord atrophy (P = 0.030). TPE is an effective treatment for steroid-refractory acute relapses of NMOSD in a multiethnic Malaysian population despite its resource-limited setting. The predictive factors of EDSSΔ6 improvement were anti-aquaporin 4 seronegativity, longer cord lesions, and higher pre-TPE EDSS. Absence of cord atrophy was predictive of better TND-based TPE response. Unexpectedly, our study showed that delayed TPE initiation of more than 14 days and up to 60 days may also be beneficial.

A pilot study on the association between SLCO1B1 RS4363657 polymorphism and muscle adverse events in adults with newly diagnosed dyslipidaemia who were prescribed a statin: the Malaysian primary health care cohort

Introduction: Statin, the first-line treatment for dyslipidaemia, may have suboptimal adherence due to its associated muscle adverse events. These data, however, remain limited.Aim: To determine the association of serum creatine kinase (CK) and SLCO1B1 rs4363657 polymorphism with statin-associated muscle adverse events (SAMAE) among dyslipidaemia participants.Methods: This was a prospective cohort study at government health clinics involving newly diagnosed adults with dyslipidaemia. SAMAE were recorded based on the patient’s complaint after a month on statin. CK was taken at baseline and follow-up. Genetic profiling was performed for SLCO1B1 rs4363657 polymorphism.Results: Among 118 participants, majority were Malay (72%) males (61%) with a mean age of 49 ± 12.2 years old and prescribed lovastatin (61.9). There was a significant association between statin types (lovastatin and simvastatin) and SAMAE (p = 0.0327); no significant association noted between CK and SAMAE (p = 0.5637). The SLCO1B1 rs4363657 polymorphism was significantly associated SAMAE (p < 0.0001).Conclusions: In this first pilot study of a multiethnic Malaysian population, the incidence of SAMAE was 18.6%. SAMAE were significantly higher in subjects on lovastatin compared to simvastatin. SLCO1B1 rs4363657 polymorphism was a significant risk factor for SAMAE.

Intron retention is among six unreported AGL mutations identified in Malaysian GSD III patients.

Glycogen storage disease type III is an autosomal recessive disorder that is caused by deficiencies of the glycogen debranching enzyme. Mutations within the AGL gene have been found to be heterogeneous, with some common mutations being reported in certain populations. The mutation spectrum of AGL gene in the multi-ethnic Malaysian population is still unknown. The present study seeks to determine the mutation spectrum of the AGL gene in Malaysian population. A total of eleven patients (eight Malay, two Chinese and one Bajau) were investigated. Genomic DNA was extracted and subsequently the AGL gene was amplified using specific primers and sequenced. Mutations found were screened in 150 healthy control samples either by restriction enzyme digestion assay or TaqMan® SNP Genotyping assay. We identified six unreported mutations (c.1423+1G>T, c.2914_2915delAA, c.3814_3815delAG, c.4333T>G, c.4490G>A, c.4531_4534delTGTC) along with three previously reported mutations (c.99C>T, c.1783C>T, c.2681+1G>A). One of the six unreported mutation causes abnormal splicing and results in retention of intron 12 of the mature transcript, while another is a termination read-through. One of the reported mutation c.2681+1G>A was recurrently found in the Malay patients (n = 7 alleles; 31.8%). The mutation spectrum of the AGL gene in Malaysian patients has shown considerable heterogeneity, and all unreported mutations were absent in all 150 healthy control samples tested.

Predictive factors of prostate cancer diagnosis with PSA 4.0–10.0 ng/ml in a multi-ethnic Asian population, Malaysia

To identify the associated factors determining prostate cancer detection using transrectal ultrasound (TRUS)-guided prostate biopsy, within a multi-ethnic Malaysian population with prostate specific antigen (PSA) between 4.0 and 10.0ng/ml. Study subjects included men with initial PSA between 4.0 and 10.0ng/ml that have undergone 12-core TRUS-guided prostate biopsy between 2009 and 2016. The prostate cancer detection rate was calculated, while potential factors associated with detection were investigated via univariable and multivariable analysis. A total of 617 men from a multi-ethnic background encompassing Chinese (63.5%), Malay (23.1%) and Indian (13.3%) were studied. The overall cancer detection rate was 14.3% (88/617), which included cancers detected at biopsy 1 (first biopsy), biopsy 2 (second biopsy with previous negative biopsy) and biopsy≥3 (third or more biopsies with prior negative biopsies). Indian men displayed higher detection rate (23.2%) and increased risk of prostate cancer development (OR 1.85, 95% CI 1.03-3.32, p<0.05), compared to their Malay (9.8%) and Chinese (14.0%) counterparts. Multivariable analysis revealed that ethnicity and PSA density (PSAD) are independent factors associated with overall prostate cancer detection rate. A unit increase of PSAD reflected an increase in PSA after controlling for prostate volume. Prostate cancer detection in Malaysia is comparatively lower. Our study suggests that ethnicity and PSA density should be considered when recommending first or repeat TRUS-guided prostate biopsy for prostate cancer detection in a multi-ethnic Malaysian population.

Diagnostic Efficacy of Synthesized 2D Digital Breast Tomosynthesis in Multi-ethnic Malaysian Population

Synthesized 2D images can be reconstructed from tomosynthesis images in breast imaging. This study aims to investigate the diagnostic efficacy of synthesized 2D images (C-View) in comparison to full field digital mammography (FFDM) when used with digital breast tomosynthesis (DBT) in multi-ethnic Malaysian population. FFDM and C-View images (n = 380) were independently evaluated by three readers through Breast Imaging Reporting and Data System (BI-RADS) categorisation, breast density and lesion characterisation. Statistical analysis was done comparing sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of C-View + DBT with FFDM + DBT as standard of reference. Very good interreader agreement in BI-RADS category and density assessment between C-View + DBT and FFDM + DBT, with high sensitivity, specificity, PPV and NPV of C-View + DBT when compared with FFDM + DBT. There was comparable PPV between C-View + DBT and FFDM + DBT, with histopathology as gold standard. High level of interreader agreement in BI-RADS category and density assessment for FFDM + DBT and C-View + DBT. There was good agreement between FFDM + DBT and C-View + DBT in mass characterization, and almost perfect agreement in calcification and asymmetric density. 52.2% lower radiation dose incurred when using C-View + DBT. Hence, synthesized 2D images are comparable to FFDM with reduction in radiation dose within the limits of Malaysian multi-ethnic population.

Prevalence and sociodemographic correlates of cervicovaginal human papillomavirus (HPV) carriage in a cross-sectional, multiethnic, community-based female Asian population

ObjectivesCervical cancer is a largely preventable disease, and the strategic implementation of a cervical cancer prevention programme is partly dependent on the impact of human papillomavirus (HPV) infection interpreted within...

Clinical Characteristics, Pain, and Quality of Life Experiences of Trigeminal Neuralgia in a Multi-Ethnic Asian Cohort.

To describe the clinical characteristics of trigeminal neuralgia (TN) in a multi-ethnic Malaysian population and to relate them to standardized measures of pain severity, anxiety, depression, and quality of life (QoL). Patients fulfilling the International Headache Society (IHS) criteria for TN were prospectively interviewed for their demographic and clinical data. Pain intensity was rated with a visual analog scale (VAS), anxiety and depression were determined by the Hospital Anxiety and Depression Scale (HADS), and QoL was assessed by the Short-Form 36 (SF-36) questionnaire. Chi-square, Mann-Whitney U, and Spearman correlation tests were used to test for differences considering a significance level of P < .05. Of the 75 included patients, 52 (69.3%) were women with a mean ± standard deviation (SD) onset age of 52.0 ± 12.7 years, and 57.3% were Chinese, 24.0% Malay, and 18.7% Indian. Pain was more common on the right side (69.3%) and in the maxillary and mandibular divisions. VAS scores for pain at its worst were higher in anxious/borderline anxious patients compared to non-anxious patients (89.5 ± 15.9 vs 80.9 ± 17.2, respectively; P < .05), and VAS scores for pain at its least were higher in depressed/borderline depressed subjects compared to non-depressed subjects (38.4 ± 25.8 vs 23.0 ± 19.2, respectively; P < .05). Chinese patients had lower VAS scores for pain at its least compared to Indian patients (19.7 ± 16.1 vs 39.9 ± 24.7; P < .01). TN patients scored lower in all eight domains of the SF-36 compared to the general population. Indian patients had lower scores in role limitations due to physical health (8.9 ± 23.2 vs 49.4 ± 43.8; P < .01) and social function (56.3 ± 13.6 vs 76.5 ± 23.6; P < .01) than Chinese patients, and Malay patients had lower mental health scores compared to Chinese patients (59.1 ± 19.5 vs 73.0 ± 21.0; P < .01). Clinical characteristics of TN patients were similar to those of other populations. There were differences in pain ratings and QoL between TN patients of different ethnicities, as well as between those with anxiety and depression.

Correlation of serum cartilage oligomeric matrix protein (COMP) and interleukin-16 (IL-16) levels with disease severity in primary knee osteoarthritis: A pilot study in a Malaysian population.

ObjectiveThe aim of this study was to investigate the correlations between serum cartilage oligomeric matrix protein (COMP), interleukin-16 (IL-16) and different grades of knee osteoarthritis (KOA) in Malaysian subjects.MethodsNinety subjects were recruited comprising 30 with Kellgren-Lawrence (K-L) grade 2 KOA, 27 with K-L grade 3 KOA, 7 with grade 4 KOA, and 30 healthy controls. All subjects completed the Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire. Serum COMP and IL-16 levels were measured using ELISA and their values log transformed to ensure a normal distribution.ResultsThere was no significant differences in levels of log serum COMP and IL-16 between healthy controls and KOA patients. There were no significant differences in the log serum COMP and IL-16 levels within the different K-L grades in the KOA patients. In KOA patients, log serum IL-16 levels significantly correlated with the WOMAC score (p = 0.001) and its subscales, pain (p = 0.005), stiffness (p = 0.019) and physical function (p<0.0001). Serum IL-16 levels were significantly higher in Malaysian Indians compared to Malays and Chinese (p = 0.024).ConclusionsIn this multi-ethnic Malaysian population, there was no difference in serum COMP and IL-16 levels between healthy controls and patients with KOA, nor was there any difference in serum COMP or IL-16 levels across the various K-L grades of KOA. However, there were significant inter-racial differences in serum IL-16 levels.

HLA-A*31: 01 and HLA-B*15:02 association with Stevens-Johnson syndrome and toxic epidermal necrolysis to carbamazepine in a multiethnic Malaysian population.

The majority of the carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis CBZ-SJS/TEN are associated with HLA-B*15:02 in Asian populations where this allele is common. In contrast, the association with HLA-A*31:01 is only reported in Japanese and Europeans. This study aimed to further investigate the association with HLA-A*31:01 besides HLA-B*15:02 in a multiethnic Malaysian population. Twenty-eight CBZ-SJS/TEN cases and 227 CBZ-tolerant controls were recruited. Association was tested by comparing carrier frequencies of the alleles between cases and controls. Significant associations were detected between HLA-B*15:02 and CBZ-SJS/TEN in independent ethnic groups: Malays [P=2.00×10; odds ratio (OR): 49.0; 95% confidence interval (CI): 9.36-256.81], Chinese (P=0.0047; OR: 14.3; 95% CI: 2.38-86.03) and Indians (P=0.04; OR: 13.8; 95% CI: 1.51-124.99). Combined analysis of all ethnic groups showed a significant association with OR Cochran-Mantel-Haenszel (ORCMH) of 26.6 (95% CI: 12.80-55.25; PCMH=2.31×10). In Indians, HLA-A*31:01 was found to be associated significantly with CBZ-SJS/TEN (P=0.023; OR: 10.4; 95% CI: 1.64-65.79) and combined analyses of both variants, HLA-A*31:01 and HLA-B*15:02, increased the strength of the association (P=0.0068; OR: 14.3; 95% CI: 2.20-92.9). Besides HLA-B*15:02, our study found a new association between HLA-A*31:01 and CBZ-SJS/TEN in Indians.

Socioeconomic and sociocultural determinants of psychological distress and quality of life among patients with psoriasis in a selected multi-ethnic Malaysian population

Patients with psoriasis may have increased risk of psychological comorbidities. This cross-sectional study aimed at determining associations between sociocultural and socioeconomic factors with the Depression Anxiety Stress Scale (DASS) scores and the Dermatology Life Quality Index (DLQI) scores. Adult patients with psoriasis were recruited from a Dermatology outpatient clinic via convenience sampling. Interviews were conducted regarding socio-demographic factors and willing subjects were requested to complete the DASS and DLQI questionnaires. The Pearson χ2 test, Fisher’s exact test and multivariate logistic regression were used for statistical analysis to determine independent predictors of depression, anxiety, stress and severe impairment of quality of life. Unadjusted analysis revealed that depression was associated with Indian ethnicity (p = .041) and severe impairment of quality of life was associated with Indian ethnicity (p = .032), higher education (p = .013), higher income (p = .042), and employment status (p = .014). Multivariate analysis revealed that Indian ethnicity was a predictor of depression (p = .024). For stress, tertiary level of education (p = .020) was an independent risk factor while a higher monthly income was a protective factor (p = .042). The ethnic Indians and Malays were significantly more likely than the ethnic Chinese to suffer reduced quality of life (p = .001 and p = .006 respectively) and subjects with tertiary education were more likely to have severe impairment of quality of life (p = .002). Our study was unique in determining sociocultural influences on psychological complications of psoriasis in a South East Asian population. This has provided invaluable insight into factors predictive of adverse effects of psoriasis on psychological distress and quality of life in our patient population. Future studies should devise interventions to specifically target at risk groups in the development of strategies to reduce morbidity associated with psoriasis.

Association of Cholesteryl Ester Transfer Protein and Endothelial Nitric Oxide Synthase Gene Polymorphisms With Coronary Artery Disease in the Multi-Ethnic Malaysian Population.

Genetic variants of cholesteryl ester transfer protein (CETP) and endothelial nitric oxide synthase (eNOS) influence high-density lipoprotein cholesterol (HDL-C) metabolism and nitric oxide (NO) synthesis, respectively, and might increase the risk of coronary artery disease (CAD). This study is to investigate the relationship between genetic polymorphisms and the risk of CAD and to evaluate their potential interactions. A total of 237 patients with CAD and 101 controls were genotyped. The association of the polymorphism with the risk of CAD varied among the ethnic groups. Moreover, the concomitant presence of both CETP B1 and eNOS 4a alleles significantly increased the risk of CAD in the Malay group (OR = 33.8, P < .001) and the Indian group (OR = 10.9, P = .031) but not in the Chinese group. This study has identified a novel ethnic-specific gene-gene interaction and suggested that the combination of CETP B1 allele and eNOS 4a allele significantly increases the risk of CAD in Malays and Indians.

Screening of Peroxisome Proliferator-Activated Receptors (PPARs) α, γ and α Gene Polymorphisms for Obesity and Metabolic Syndrome Association in the Multi-Ethnic Malaysian Population.

This study aimed to investigate the association of peroxisome proliferator-activated receptor (PPAR) genes PPARα L162V, PPARγ2 C161T and PPARδ T294C single nucleotide polymorphisms (SNPs) with obesity and metabolic syndrome (Met-S) in a multi-ethnic population in Kampar, Malaysia. Socio-demographic data, anthropometric and biochemical measurements (plasma lipid profile, adiponectin and interleukin-6 [IL-6] levels) were taken from 307 participants (124 males; 180 obese; 249 Met-S; 97 Malays, 85 ethnic Chinese, 55 ethnic Indians). The overall minor allele frequencies were .08, .22 and .30 for PPAR α L162V, γ C161T, δ T294C, respectively. All SNPs were not associated with obesity, Met-S and obesity with/without Met-S by χ(2) analysis, ethnicity-stratified and logistic regression analyses. Nevertheless, participants with V162 allele of PPARα had significantly higher IL-6, while those with T161 allele of PPARγ2 had significantly lower HOMA-IR. All PPAR SNPs were not associated with obesity and Met-S in the suburban population of Kampar, Malaysia, where only PPARα V162 and PPARγ2 T161 alleles were associated with plasma IL-6 and HOMA-IR, respectively.