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1.  Unravelling the Genetic History of Negritos and Indigenous Populations of Southeast Asia 
Genome Biology and Evolution  2015;7(5):1206-1215.
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.
PMCID: PMC4453060  PMID: 25877615
Negritos; Senoi; Proto-Malay; population genetics; SNPs
2.  Clinical manifestation and sensitization of allergic children from Malaysia 
Asia Pacific Allergy  2015;5(2):78-83.
An epidemiological rise of allergic diseases in developing countries raises new challenges. Currently a paucity of data exists describing allergy symptomology and sensitization to common food and aeroallergens in young children from developing countries.
To compare changes in symptomology, food allergen sensitization and aeroallergen sensitization in a cross-sectional study of children <2 years and 2-10 years.
A total of 192 allergic children (aged <2 years, 35 children; aged 2-10 years, 157 children) underwent specific IgE (>0.35 kU/L) to common food (egg white, cow's milk, cod fish, wheat, peanut, soya, peanut, and shrimp) and house dust mites (Dermatophagoides pteronyssinus and Blomia tropicalis).
In children <2 years, atopic dermatitis (65.7%) was the most common symptom whereas in children 2-10 years it was rhinoconjunctivitis (74.5%). Higher sensitization rate to eggs (p < 0.01) and cow's milk (p = 0.044) was seen in <2 years group when compared to the 2-10 years group, but no significant differences for shrimp (p = 0.29), wheat (p = 0.23) and soya (p = 0.057). Interestingly, sensitization to peanut (p = 0.012) and fish (p = 0.035) was significantly decreased in the 2-10 years group. Sensitization to house dust mites (p < 0.01) dramatically increased in the older children.
Our study supports concept of atopic march from a developing country like Malaysia.
PMCID: PMC4415183  PMID: 25938072
Hypersensitivity; Allergens; Asia; Food; Pyroglyphidae
3.  Cardio-metabolic health risks in indigenous populations of Southeast Asia and the influence of urbanization 
BMC Public Health  2015;15:47.
South East Asia (SEA) is home to over 30 tribes of indigenous population groups who are currently facing rapid socio-economic change. Epidemiological transition and increased prevalence of non-communicable diseases (NCD) has occured. In Peninsular Malaysia, the Orang Asli (OA) indigenous people comprise 0 · 6% (150,000) of the population and live in various settlements. OA comprise three distinct large tribes with smaller sub-tribes. The three large tribes include Proto-Malay (sub-tribes: Orang Seletar and Jakun), Senoi (sub-tribes: Mahmeri and Semai), and Negrito (sub-tribes: Jehai, Mendriq and Batek).
We studied the health of 636 OA from seven sub-tribes in the Peninsular. Parameters that were assessed included height, weight, BMI and waist circumference whilst blood pressure, cholesterols, fasting blood glucose and HbA1c levels were recorded. We then analysed cardio-metabolic risk factor prevalences and performed multiple pair-wise comparisons among different sub-tribes and socio-economic clusters.
Cardio-metabolic risk factors were recorded in the seven sub-tribes.. Prevalence for general and abdominal obesity were highest in the urbanized Orang Seletar (31 · 6 ± 5 · 7%; 66 · 1 ± 5 · 9%). Notably, hunter gatherer Jehai and Batek tribes displayed the highest prevalence for hypertension (43 · 8 ± 9 · 29% and 51 · 2 ± 15 · 3%) despite being the leanest and most remote, while the Mendriq sub-tribe, living in the same jungle area with access to similar resources as the Batek were less hypertensive (16.3 ± 11.0%), but displayed higher prevalence of abdominal obesity (27.30 ± 13.16%).
We describe the cardio-metabolic risk factors of seven indigenous communities in Malaysia. We report variable prevalence of obesity, cholesterol, hypertension and diabetes in the OA in contrast to the larger ethnic majorities such as Malays, Chinese and Indians in Malaysia These differences are likely to be due to socio-economic effects and lifestyle changes. In some sub-tribes, other factors including genetic predisposition may also play a role. It is expected that the cardio-metabolic risk factors may worsen with further urbanization, increase the health burden of these communities and strain the government’s resources.
PMCID: PMC4314805  PMID: 25636170
4.  Polymorphic variants of interleukin-13 R130Q, interleukin-4 T589C, interleukin-4RA I50V, and interleukin-4RA Q576R in allergic rhinitis: A pilot study 
Allergy & Rhinology  2012;3(1):e35-e40.
The development of allergic rhinitis is considered to be caused by the complex interactions between genetic predisposition and environmental factors. Polymorphisms in the interleukin (IL)-13/4/4RA pathway have previously been shown to be associated with atopic diseases. The purpose of this study was to determine the association between IL-13 R130Q, IL-4 T589C, IL4 receptor alpha (IL-4RA) I50V, or IL-4RA Q576R polymorphisms and risk of allergic rhinitis in a hospital-based Malaysian population. A case-control pilot study was undertaken and genotyping of these polymorphisms was performed using polymerase chain reaction–restriction fragment length polymorphism on 54 allergic rhinitis patients and 45 healthy individuals. Polymorphism of IL-13 R130Q showed significant difference in genotype (p = 0.048) and allele (p = 0.002) frequencies in allergic rhinitis when compared with healthy controls. Individuals who were GA heterozygotes (adjusted odds ratio [ORadj] = 3.567; 95% CI, 1.211–10.509), and carriers of A allele genotype (ORadj = 3.686; 95% CI, 1.300–10.451) and A allele (ORadj = 3.071; 95% CI, 1.514–6.232) had an elevated risk of developing allergic rhinitis. The genotype and allele frequencies of IL-4 T589C, IL-4RA I50V, and IL-4RA Q576R polymorphisms were not significantly different between the allergic rhinitis patients and normal healthy individuals and did not show an associated risk with allergic rhinitis. Our findings indicate that polymorphic variant of IL-13 R130Q appears to be associated with increased risk for development of allergic rhinitis in a hospital-based Malaysian population but not IL-4 T589C, IL-4RA I50V, and IL-4RA Q576 polymorphisms. Additional studies using larger sample size are required to confirm our findings and its exact role in allergic rhinitis.
PMCID: PMC3404476  PMID: 22852128
Allele; allergy; RFLP; genotyping; IL-13; IL-4; IL-4RA; PCR; polymorphism; rhinitis
5.  Inhibitory activities of microalgal extracts against Epstein-Barr virus DNA release from lymphoblastoid cells*  
This study aimed to assess the inhibitory activities of methanol extracts from the microalgae Ankistrodesmus convolutus, Synechococcus elongatus, and Spirulina platensis against Epstein-Barr virus (EBV) in three Burkitt’s lymphoma (BL) cell lines, namely Akata, B95-8, and P3HR-1. The antiviral activity was assessed by quantifying the cell-free EBV DNA using real-time polymerase chain reaction (PCR) technique. The methanol extracts from Ankistrodesmus convolutus and Synechococcus elongatus displayed low cytotoxicity and potent effect in reducing cell-free EBV DNA (EC50<0.01 µg/ml) with a high therapeutic index (>28 000). After fractionation by column chromatography, the fraction from Synechococcus elongatus (SEF1) reduced the cell-free EBV DNA most effectively (EC50=2.9 µg/ml, therapeutic index>69). Upon further fractionation by high performance liquid chromatography (HPLC), the sub-fraction SEF1’a was most active in reducing the cell-free EBV DNA (EC50=1.38 µg/ml, therapeutic index>14.5). This study suggests that microalgae could be a potential source of antiviral compounds that can be used against EBV.
PMCID: PMC3087089  PMID: 21528487
Microalgae; Ankistrodesmus convolutus; Synechococcus elongatus; Spirulina platensis; Lymphoblastoid cells; Epstein-Barr virus (EBV)

Results 1-5 (5)