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Fulltext Natural selection and local adaptation of blood pressure regulation and their perspectives on precision medicine in hypertension

Hoh BP, Abdul Rahman T, Yusoff K

Hereditas, 2019;156:1.
PMID: 30636949 DOI: 10.1186/s41065-019-0080-1

Prevalence of hypertension (HTN) varies substantially across different populations. HTN is not only common - affecting at least one third of the world's adult population - but is also the most important driver for cardiovascular diseases. Yet up to a third of hypertensive patients are resistant to therapy, contributed by secondary hypertension but more commonly the hitherto inability to precisely predict response to specific antihypertensive agents. Population and individual genomics information could be useful in guiding the selection and predicting the response to treatment - an approach known as precision medicine. However this cannot be achieved without the knowledge of genetic variations that influence blood pressure (BP). A number of evolutionary factors including population demographics and forces of natural selection may be involved. This article explores some ideas on how natural selection influences BP regulation in ethnically and geographically diverse populations that could lead to them being susceptible to HTN. We explore how such evolutionary factors could impact the implementation of precision medicine in HTN. Finally, in order to ensure the success of precision medicine in HTN, we call for more initiatives to understand the genetic architecture within and between diverse populations with ancestry from different parts of the world, and to precisely classify the intermediate phenotypes of HTN.
Fulltext The Peopling and Migration History of the Natives in Peninsular Malaysia and Borneo: A Glimpse on the Studies Over the Past 100 years

Hoh BP, Deng L, Xu S

Front Genet, 2022;13:767018.
PMID: 35154269 DOI: 10.3389/fgene.2022.767018

Southeast Asia (SEA) has one of the longest records of modern human habitation out-of-Africa. Located at the crossroad of the mainland and islands of SEA, Peninsular Malaysia is an important piece of puzzle to the map of peopling and migration history in Asia, a question that is of interest to many anthropologists, archeologists, and population geneticists. This review aims to revisit our understanding to the population genetics of the natives from Peninsular Malaysia and Borneo over the past century based on the chronology of the technology advancement: 1) Anthropological and Physical Characterization; 2) Blood Group Markers; 3) Protein Markers; 4) Mitochondrial and Autosomal DNA Markers; and 5) Whole Genome Analysis. Subsequently some missing gaps of the study are identified. In the later part of this review, challenges of studying the population genetics of natives will be elaborated. Finally, we conclude our review by reiterating the importance of unveiling migration history and genetic diversity of the indigenous populations as a steppingstone towards comprehending disease evolution and etiology.
Microsatellite instability and loss of heterozygosity in oral squamous cell carcinoma in Malaysian population

Ashazila MJ, Kannan TP, Venkatesh RN, Hoh BP

Oral Oncol, 2011 May;47(5):358-64.
PMID: 21450513 DOI: 10.1016/j.oraloncology.2011.03.005

Loss of heterozygosity (LOH) and microsatellite instability (MSI) have been documented as important events in oral squamous cell carcinoma (OSCC). Five microsatellite markers D3S192, D3S966, D3S647, D3S1228 and D3S659 were selected on chromosome 3p because of high frequency of alterations reported in head and neck squamous cell carcinoma and the involvement of von Hippel Lindau (VHL) at 3p25-26 and the fragile histidine triad (FHIT) at 3p14.2 genes proven in many tumour types. A total of 50 archival tissue samples of OSCC and corresponding normal samples were analyzed for LOH and MSI status. The overall LOH for the markers selected on 3p was 56 out of 189 informative cases (29.6%). The most frequent LOH was identified for the marker D3S966 which was 18/42 (42.8%) of informative cases suggesting the presence of putative tumour suppressor genes (TSGs) in this loci. In this study, high frequency of microsatellite instability was found in D3S966 which was 28.6% of informative cases; this reveals the possibility of mutations of MMR genes in this region. Frequent microsatellite alterations (MA) were observed in 3 markers D3S966 (71.4%), D3S1228 (56.7%) and D3S192 (41.0%). There was no significant association between LOH with gender, tumour stages and differentiation grades. However, there was a significant association between tumour stage and differentiation grades with MSI status in OSCC in Malaysian population with p values of 0.002 and 0.035, respectively. There was also a significant association between MA and differentiation grades (p=0.041).
Isolation of trinucleotide microsatellite markers for Mystus nemurus

Hoh BP, Siraj SS, Tan SG, Yusoff K

Genetika, 2008 Mar;44(3):427-9.
PMID: 18664151

Twelve single locus trinucleotide microsatellite markers were developed to characterize the Asian river catfish, Mystus nemurus, an important food fish in South East Asia. They were obtained by using a rapid method namely the 5' anchored PCR enrichment protocol. The specific primers were designed to flank the repeat sequences and these were subsequently used to characterize 90 unrelated fish from Malaysia. The number of alleles per locus ranged from 2 (MnVj2-281) to 12 (MnBp8-4-43b) while the levels of heterozygosity ranged from 0.0444 (MnVj2-1-19) to 0.7458 (MnVj2-291).
Fulltext Segregation and genetic linkage analyses of river catfish, Mystus nemurus, based on microsatellite markers

Hoh BP, Siraj SS, Tan SG, Yusoff K

Genet. Mol. Res., 2013;12(3):2578-93.
PMID: 23479146 DOI: 10.4238/2013.February.28.1

The river catfish Mystus nemurus is an important fresh water species for aquaculture in Malaysia. We report the first genetic linkage map of M. nemurus based on segregation analysis and a linkage map using newly developed microsatellite markers of M. nemurus. A total of 70 of the newly developed polymorphic DNA microsatellite markers were analyzed on pedigrees generated using a pseudo-testcross strategy from 2 mapping families. In the first mapping family, 100 offspring were produced from randomly selected dams of the same populations; dams of the second family were selected from 2 different populations, and this family had 50 offspring. Thirty-one of the 70 markers segregated according to the Mendelian segregation ratio. Linkage analysis revealed that 17 microsatellite markers belonging to 7 linkage groups were obtained at a logarithm of the odds score of 1.2 spanning 584 cM by the Kosambi mapping function, whereas the other 14 remained unlinked. The results from this study will act as primer to a more extensive genetic mapping study aimed towards identifying genetic loci involved in determining economically important traits.
Fulltext Homozygous familial hypercholesterolemia

Alicezah MK, Razali R, Rahman T, Hoh BP, Suhana NH, Muid S, et al.

Malays J Pathol, 2014 Aug;36(2):131-7.
PMID: 25194536 MyJurnal

We report a rare case of homozygous familial hypercholesterolemia (HoFH), a 22-year-old Malay woman who presented initially with minor soft tissue injury due to a cycling accident. She was then incidentally found to have severe xanthelasma and hypercholesterolemia (serum TC 15.3 mmol/L and LDL-C 13.9 mmol/L). She was referred to the Specialized Lipid Clinic and was diagnosed with familial hypercholesterolemia (FH) based on the Simon Broome (SB) diagnostic criteria. There was a family history of premature coronary heart disease (CHD) in that three siblings had sudden cardiac death, and of consanguineous marriage in that her parents are cousins. DNA screening of LDLR and APOB genes was done by Polymerase Chain Reaction (PCR), followed by Denaturing High Performance Liquid Chromatography (DHPLC). Homozygous mutation C255S in Exon 5 of her LDLR gene was found. There was no mutation was found in Exon 26 and Exon 29 of the APOB gene. This report is to emphasize the importance of identifying patients with FH and cascade screening through established diagnostic criteria and genetic studies in order to ensure early detection and early treatment intervention to minimize the risk of developing CHD and related complications.
Fulltext A novel rare copy number variant of the ABCF1 gene identified among dengue fever patients from Peninsular Malaysia

Hoh BP, Sam SS, Umi SH, Mahiran M, Nik Khairudin NY, Rafidah Hanim S, et al.

Genet. Mol. Res., 2014;13(1):980-5.
PMID: 24634119 DOI: 10.4238/2014.February.19.9

Copy number variation (CNV) is a form of genetic variation in addition to single nucleotide polymorphisms. The significance of CNV in the manifestation of a number of diseases is only recently receiving considerable attention. We genotyped 163 dengue patients from Peninsular Malaysia for genes possibly linked to dengue infection using quantitative real-time PCR. Here, we report a serendipitous discovery of a novel rare CNV of the ABCF1 gene among the dengue patients. Among these patients, two had a gain of 1 copy (CN = 3) and one had lost 1 copy (CN = 1), indicating that a rare CNV of the ABCF1 gene was detected among dengue patients from Peninsular Malaysia. Although the gene is suspected to regulate inflammatory responses and pathogen-induced cytokine storm, its relevance to dengue requires further investigation.
An improved rapid genotyping method for the study of beta-2 adrenergic receptor gene polymorphisms using single tube allele specific multiplex PCR

Zilfalil BA, Hoh BP, Nizam MZ, Liza-Sharmini AT, Teh LK, Ismail R

J Clin Pharm Ther, 2006 Dec;31(6):637-40.
PMID: 17176369

Seventeen single nucleotide polymorphisms (SNPs) have been identified so far, within the beta-2 receptor (beta(2) AR) gene. The presence of so many SNPs within the beta(2) AR gene causes a problem, for those studying beta(2) AR pharmacogenetics, in relation to which SNPs to choose. Most of the work has focused on the three common SNPs within the coding block (alleles 16, 27 and 164) and the techniques developed have been for these three functionally important alleles.
Fulltext Somatic copy-neutral loss of heterozygosity and copy number abnormalities in Malaysian sporadic colorectal carcinoma patients

Yam YY, Hoh BP, Othman NH, Hassan S, Yahya MM, Zakaria Z, et al.

Genet. Mol. Res., 2013;12(1):319-27.
PMID: 23420356 DOI: 10.4238/2013.February.7.1

Colorectal cancer is one of the most common cancers in many countries, including Malaysia. The accumulation of genomic alterations is an important feature of colorectal carcinogenesis. A better understanding of the molecular events underlying the stages of colorectal carcinogenesis might be helpful in the detection and management of the disease. We used a commercially available single-nucleotide polymorphism genotyping array to detect both copy number abnormalities (CNAs) and copy-neutral loss of heterozygosity (LOH) in sporadic colorectal carcinomas. Matched tumor and normal tissues of 13 colorectal carcinomas (Dukes' stages A-D) were analyzed using a 250K single nucleotide polymorphism array. An additional assay was performed to determine the microsatellite instability status by using the National Cancer Institute-recommended BAT-26 panel. In general, copy number gain (92.3%) was most common, followed by copy number loss (53.8%) and copy-neutral LOH (46.2%). Frequent CNAs of gains and losses were observed on chromosomes 7p, 8, 13q, 17p, 18q, and 20q, and copy-neutral LOH was observed on chromosomes 2, 6, 12, 13q, 14q, 17, 20p, 19q, and 22q. Even though genomic alterations are associated with colorectal cancer progression, our results showed that DNA CNAs and copy-neutral LOH do not reflect disease progression in at least 50% tumors. Copy-neutral LOH was observed in both early and advanced tumors, which favors the involvement of these genomic alterations in the early stages of tumor development.
Fulltext An alternate method for DNA and RNA extraction from clotted blood

Zakaria Z, Umi SH, Mokhtar SS, Mokhtar U, Zaiharina MZ, Aziz AT, et al.

Genet. Mol. Res., 2013;12(1):302-11.
PMID: 23408417 DOI: 10.4238/2013.February.4.4

We developed an alternative method to extract DNA and RNA from clotted blood for genomic and molecular investigations. A combination of the TRIzol method and the QIAamp spin column were used to extract RNA from frozen clotted blood. Clotted blood was sonicated and then the QIAamp DNA Blood Mini Kit was used for DNA extraction. Extracted DNA and RNA were adequate for gene expression analysis and copy number variation (CNV) genotyping, respectively. The purity of the extracted RNA and DNA was in the range of 1.8-2.0, determined by absorbance ratios of A(260):A(280). Good DNA and RNA integrity were confirmed using gel electrophoresis and automated electrophoresis. The extracted DNA was suitable for qPCR and microarrays for CNV genotyping, while the extracted RNA was adequate for gene analysis using RT-qPCR.
Fulltext Unravelling the genetic history of Negritos and indigenous populations of Southeast Asia

Aghakhanian F, Yunus Y, Naidu R, Jinam T, Manica A, Hoh BP, et al.

Genome Biol Evol, 2015 May;7(5):1206-15.
PMID: 25877615 DOI: 10.1093/gbe/evv065

Indigenous populations of Malaysia known as Orang Asli (OA) show huge morphological, anthropological, and linguistic diversity. However, the genetic history of these populations remained obscure. We performed a high-density array genotyping using over 2 million single nucleotide polymorphisms in three major groups of Negrito, Senoi, and Proto-Malay. Structural analyses indicated that although all OA groups are genetically closest to East Asian (EA) populations, they are substantially distinct. We identified a genetic affinity between Andamanese and Malaysian Negritos which may suggest an ancient link between these two groups. We also showed that Senoi and Proto-Malay may be admixtures between Negrito and EA populations. Formal admixture tests provided evidence of gene flow between Austro-Asiatic-speaking OAs and populations from Southeast Asia (SEA) and South China which suggest a widespread presence of these people in SEA before Austronesian expansion. Elevated linkage disequilibrium (LD) and enriched homozygosity found in OAs reflect isolation and bottlenecks experienced. Estimates based on Ne and LD indicated that these populations diverged from East Asians during the late Pleistocene (14.5 to 8 KYA). The continuum in divergence time from Negritos to Senoi and Proto-Malay in combination with ancestral markers provides evidences of multiple waves of migration into SEA starting with the first Out-of-Africa dispersals followed by Early Train and subsequent Austronesian expansions.
Hepatitis B virus infection: Epidemiology and seroprevalence rate amongst Negrito tribe in Malaysia

Sahlan N, Fadzilah MN, Muslim A, Shaari SA, Abdul Rahman T, Hoh BP

Med J Malaysia, 2019 08;74(4):320-325.
PMID: 31424040

INTRODUCTION: Prevalence of Hepatitis B virus (HBV) infection among the non-indigenous people in Malaysia has been well established and range between 3% and 5%. However, data from the indigenous (Orang Asli) people is still lacking. The Negrito population is the most remotely located Orang Asli tribe with limited access to health care facilities. This study was undertaken to determine the epidemiology and seroprevalence of HBV infection among the Negrito.
METHODS: Surveys were conducted in five Negrito settlements in Kelantan and Perak states in Malaysia. A total of 150 participants were recruited. Clinical history was taken and physical examination was performed. Five millilitres of whole blood were collected and tested for hepatitis B surface antigen (HBsAg) using electrochemiluminescence immunoassay.
RESULTS: Participants were mainly from the Bateq (49.3%) and Mendriq (29.4%) sub-tribes. Overall, 13 subjects (8.7 %); nine males and four females were HBsAg positive. Nine of the HBsAg positive subjects were ≥35 years old. All of them had history of home deliver without evidence of antenatal record. Six (46%) of the HBsAg positive subjects had tattoo and body piercing in the past.
CONCLUSION: The prevalence of HBV infection rate amongst the Negrito tribe is almost three-fold compared to the national rates. The reason for this finding remains unclear. Tattooing, body piercing and vertical transmission could be the main possible routes of transmission of HBV among the Negrito population in Malaysia.
Fulltext Current Status and Future Perspectives about Molecular Biomarkers of Nasopharyngeal Carcinoma

Siak PY, Khoo AS, Leong CO, Hoh BP, Cheah SC

Cancers (Basel), 2021 Jul 12;13(14).
PMID: 34298701 DOI: 10.3390/cancers13143490

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy that shows a remarkable ethnic and geographical distribution. It is one of the major public health problems in some countries, especially Southern China and Southeast Asia, but rare in most Western countries. Multifactorial interactions such as Epstein-Barr virus infection, individual's genetic susceptibility, as well as environmental and dietary factors may facilitate the pathogenesis of this malignancy. Late presentation and the complex nature of the disease have led it to become a major cause of mortality. Therefore, an effective, sensitive, and specific molecular biomarker is urgently needed for early disease diagnosis, prognosis, and prediction of metastasis and recurrence after treatment. In this review, we discuss the recent research status of potential biomarker discovery and the problems that need to be explored further for better NPC management. By studying the aberrant pattern of these candidate biomarkers that promote NPC development and progression, we are able to understand the complexity of this malignancy better, hence positing our stands better towards strategies that may provide a way forward to the discovery of more reliable and specific biomarkers for diagnosis and targeted therapeutic development.
A genome-wide characterization of copy number variations in native populations of Peninsular Malaysia

Fu R, Mokhtar SS, Phipps ME, Hoh BP, Xu S

Eur J Hum Genet, 2018 06;26(6):886-897.
PMID: 29476164 DOI: 10.1038/s41431-018-0120-8

Copy number variations (CNVs) are genomic structural variations that result from the deletion or duplication of large genomic segments. The characterization of CNVs is largely underrepresented, particularly those of indigenous populations, such as the Orang Asli in Peninsular Malaysia. In the present study, we first characterized the genome-wide CNVs of four major native populations from Peninsular Malaysia, including the Malays and three Orang Asli populations; namely, Proto-Malay, Senoi, and Negrito (collectively called PM). We subsequently assessed the distribution of CNVs across the four populations. The resulting global CNV map revealed 3102 CNVs, with an average of more than 100 CNVs per individual. We identified genes harboring CNVs that are highly differentiated between PM and global populations, indicating that these genes are predominantly enriched in immune responses and defense functions, including APOBEC3A_B, beta-defensin genes, and CCL3L1, followed by other biological functions, such as drug and toxin metabolism and responses to radiation, suggesting some attributions between CNV variations and adaptations of the PM groups to the local environmental conditions of tropical rainforests.
Fulltext Prevalence, intensity and associated risk factors of soil transmitted helminth infections: A comparison between Negritos (indigenous) in inland jungle and those in resettlement at town peripheries

Muslim A, Mohd Sofian S, Shaari SA, Hoh BP, Lim YA

PLoS Negl Trop Dis, 2019 Apr;13(4):e0007331.
PMID: 31009476 DOI: 10.1371/journal.pntd.0007331

BACKGROUND: Formerly known as the Malaysian hunter gatherers, the Negrito Orang Asli (OA) were heavily dependent on the forest for sustenance and early studies indicated high prevalence of intestinal parasitism. Initiation of a redevelopment program in the 1970s aimed to demarginalize the OA was expected to reduce soil transmitted helminth (STH) infections. Gradually, the OA were relocated to new resettlement areas at the peripheries. The aim of this study was to compare STH infections between Negritos who are still living in the inland jungle with those living in resettlements.
METHODOLOGY/PRINCIPAL FINDINGS: A total of 416 Negrito participants were grouped into two categories of communities based on location; Inland Jungle Villages (IJV); and Resettlement Plan Scheme (RPS). Iodine wet mount, formalin-ether sedimentation, modified Trichrome and modified Ziehl-Neelsen staining and Kato-Katz methods were performed on stool samples. A questionnaire was used to collect information regarding demographic, socioeconomic, environmental and hygiene behaviors. Prevalence of STH was significantly higher in IJV (91.3%) versus RPS (83.1%) (P = 0.02). However, the percentage of individuals with severe intensity of Trichuris trichiura infections was significantly higher in the RPS (17.2%) compared to IJV (6.5%) (P = 0.01). Severe Ascaris lumbricoides infection was observed at 20.0% amongst RPS Negritos and 15.0% amongst IJV (P = 0.41). Whilst for hookworm infection, both prevalence and individuals with moderate to severe infections were higher in the IJV (26.2%, 41.0%) versus RPS (18.7%, 24.0%) (P values = 0.08, 0.09), accordingly. The prevalence other intestinal parasitic infections (e.g. Entamoeba sp., Blastocystis and flukes) was also higher in IJV versus RPS. Apart from poor hygienic behaviors as significant risk factors in both communities, low socio-economic status was highly associated with STH infections in RPS (P<0.001) but not significantly associated in IJV.
CONCLUSIONS: The findings showed that ex situ development plan by RPS has not profoundly contributed to the STH reduction among the OA. Conversely, burden rate of T. trichiura infections increased due to their extreme poverty and poor hygienic behaviors. Here, we are suggesting biannual mass albendazole intervention (triple dose regimens in RPS, but a single dose in IJV) and community empowerment to both communities. For a long-term and better uptake, these strategies must be done together with the community input and participation, respecting their traditional customs and accompanied by recruitment of more OA people in the health-care taskforce.
Fulltext Screening of dystrophin gene deletions in Malaysian patients with Duchenne muscular dystrophy

Marini M, Salmi AA, Watihayati MS, SMardziah MD, Zahri MK, Hoh BP, et al.

Med J Malaysia, 2008 Mar;63(1):31-4.
PMID: 18935728 MyJurnal

Duchenne Muscular Dystrophy (DMD) is an X-linked recessive genetic disorder characterized by rapidly progressive muscle weakness. The disease is caused by deletion, duplication or point mutation of the dystrophin gene, located on the X chromosome (Xp21). Deletion accounts for 60% of the mutations within the 79 exons of the dystrophin gene. Seven exons (43, 44, 45, 46, 49, 50, and 51) were found to be most commonly deleted among the Asian patients. To detect the frequency of deletion of these 7 exons in Malaysian DMD patients, we carried out a molecular genetic analysis in 20 Malaysian DMD patients. The mean age of initial presentation was 60 months (SD 32 months, range 5-120 months). Fourteen patients were found to have deletion of at least one of the seven exons. The remaining six patients did not show any deletion on the tested exons. Deletions of exons 49, 50 and 51 were the most frequent (71.43%) and appear to be the hot spots in our cohort of patients.
Fulltext Effect of DNase treatment on RNA extraction from preimplantation murine embryos

Norhazlin J, Nor-Ashikin MN, Hoh BP, Sheikh Abdul Kadir SH, Norita S, Mohd-Fazirul M, et al.

Genet. Mol. Res., 2015;14(3):10172-84.
PMID: 26345954 DOI: 10.4238/2015.August.28.1

The quality of RNA is crucial when performing microarray experiments. This is particularly important when dealing with preimplantation embryos, from which a minimum yield of RNA of good quality can be produced. We report the optimization of several RNA extraction methods applied to preimplantation embryos at different stages of development. The quality of the samples was confirmed using a microarray and reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) analysis. A total of 30 cultured two-cell stage embryos of ICR mice were pooled at the 8-cell, morula, and blastocyst stages. The embryos were divided into two groups comprising DNase-treated and non-DNase-treated RNA samples. Total RNA was extracted using a Pico Pure RNA Isolation Kit following the manufacturer protocol, with some modifications. Lysed samples were bound to a silica-based filter, treated with deoxyribonuclease I (DNase I), and washed several times before elution. RNA concentration and integrity were evaluated using an Agilent 2100 Bioanalyzer and an RNA 6000 Pico Assay kit. Although concentrations of non-DNase-treated RNAs were higher than DNase-treated RNA, DNase-treated RNA gave a higher RNA integrity number compared with non-DNase-treated RNA. Inclusion of DNase treatment in the RNA extraction procedure gave the best quality RNA samples from preimplantation embryos, as validated by microarray and RT-qPCR quality control.
Fulltext Common variants of chemokine receptor gene CXCR3 and its ligands CXCL10 and CXCL11 associated with vascular permeability of dengue infection in peninsular Malaysia

Hoh BP, Umi-Shakina H, Zuraihan Z, Zaiharina MZ, Rafidah-Hanim S, Mahiran M, et al.

Hum Immunol, 2015 Jun;76(6):421-6.
PMID: 25858769 DOI: 10.1016/j.humimm.2015.03.019

Dengue causes significantly more human disease than any other arboviruses. It causes a spectrum of illness, ranging from mild self-limited fever, to severe and fatal dengue hemorrhagic fever, as evidenced by vascular leakage and multifactorial hemostatic abnormalities. There is no specific treatment available till date. Evidence shows that chemokines CXCL10, CXCL11 and their receptor CXCR3 are involved in severity of dengue, but their genetic association with the susceptibility of vascular leakage during dengue infection has not been reported. We genotyped 14 common variants of these candidate genes in 176 patients infected with dengue. rs4859584 and rs8878 (CXCL10) were significantly associated with vascular permeability of dengue infection (P<0.05); while variants of CXCL11 showed moderate significance of association (P=0.0527). Haplotype blocks were constructed for genes CXCL10 and CXCL11 (5 and 7 common variants respectively). Haplotype association tests performed revealed that, "CCCCA" of gene CXCL10 and "AGTTTAC" of CXCL11 were found to be significantly associated with vascular leakage (P=0.0154 and 0.0366 respectively). In summary, our association study further strengthens the evidence of the involvement of CXCL10 and CXCL11 in the pathogenesis of dengue infection.
Metabolic syndrome and cardiometabolic risk factors among indigenous Malaysians

Aghakhanian F, Wong C, Tan JSY, Yeo LF, Ramadas A, Edo J, et al.

Public Health, 2019 Nov;176:106-113.
PMID: 30509859 DOI: 10.1016/j.puhe.2018.10.001

OBJECTIVES: This study was undertaken to investigate the occurrence of metabolic syndrome (MetS) and cardiovascular disease (CVD) risk in Orang Asli (OA), the indigenous people of Peninsular Malaysia. OA consist of Negrito, Proto-Malay, and Senoi groups who collectively comprise only 0.76% of the population of Peninsular Malaysia. Owing to the challenges in accessing their remote villages, these groups are often excluded in larger government health surveys. Although tropical diseases were scourges in the past, with rapid national development, many OA communities have been gradually urbanized. We believe an epidemiological transition is occurring and non-communicable diseases are on the rise.
STUDY DESIGN: A retrospective cross-sectional study.
METHODS: Indigenous Malaysians (n = 629) from three major groups (Negrito, Proto-Malay, and Senoi) were recruited, after ethics approval and informed consent. Body mass index (BMI), body weight, height, waist circumference, and systolic and diastolic blood pressure were measured, and participants were examined for acanthosis nigricans. Venous blood samples were used for measurements of fasting blood sugar, triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Insulin resistance was estimated using a surrogate measurement TG/HDL-C. The ratios of TC to HDL-C, and of LDL-C to HDL-C were determined. MetS was accessed according to the Joint Interim Statement of the IDF Tsak Force on Epidemiology and Prevention.
RESULTS: MetS affected 29.57% of the OA population investigated and was significantly more prevalent (P
Fulltext Observational study of the status of coronary risk biomarkers among Negritos with metabolic syndrome in the east coast of Malaysia

Mokhsin A, Mokhtar SS, Mohd Ismail A, M Nor F, Shaari SA, Nawawi H, et al.

BMJ Open, 2018 12 04;8(12):e021580.
PMID: 30518581 DOI: 10.1136/bmjopen-2018-021580

OBJECTIVES: To determine the prevalence of metabolic syndrome (MS), ascertain the status of coronary risk biomarkers and establish the independent predictors of these biomarkers among the Negritos.
SETTINGS: Health screening programme conducted in three inland settlements in the east coast of Malaysia and Peninsular Malaysia.
SUBJECTS: 150 Negritos who were still living in three inland settlements in the east coast of Malaysia and 1227 Malays in Peninsular Malaysia. These subjects were then categorised into MS and non-MS groups based on the International Diabetes Federation (IDF) consensus worldwide definition of MS and were recruited between 2010 and 2015. The subjects were randomly selected and on a voluntary basis.
PRIMARY AND SECONDARY OUTCOME MEASURES: This study was a cross-sectional study. Serum samples were collected for analysis of inflammatory (hsCRP), endothelial activation (sICAM-1) and prothrombogenesis [lp(a)] biomarkers.
RESULTS: MS was significantly higher among the Malays compared with Negritos (27.7%vs12.0%). Among the Malays, MS subjects had higher hsCRP (p=0.01) and sICAM-1 (p<0.05) than their non-MS counterpart. There were no significant differences in all the biomarkers between MS and the non-MS Negritos. However, when compared between ethnicity, all biomarkers were higher in Negritos compared with Malays (p<0.001). Binary logistic regression analysis affirmed that Negritos were an independent predictor for Lp(a) concentration (p<0.001).
CONCLUSIONS: This study suggests that there may possibly be a genetic influence other than lifestyle, which could explain the lack of difference in biomarkers concentration between MS and non-MS Negritos and for Negritos predicting Lp(a).

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