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  1. Lim JJ, Reginald K, Say YH, Liu MH, Chew FT
    Int Arch Allergy Immunol, 2023;184(10):975-984.
    PMID: 37393903 DOI: 10.1159/000530948
    INTRODUCTION: Frequent dietary patterns for fast food diets are suggested to be a risk factor for atopic disease development. Excessive dietary fats in fast foods are postulated to promote low-grade chronic inflammation. However, no studies in Asia have yet to characterize the dietary pattern for high-fat foods with atopic diseases. Thus, this study aims to assess the association between dietary fats with the prevalence of atopic diseases in an allergic cohort.

    METHODS: Through an investigator-administered questionnaire that follows the International Study of Asthma and Allergies in Childhood (ISAAC) protocol, we evaluated the eating habits, lifestyle behaviours, sociodemographics, and atopic symptoms, and history among 11,494 young Chinese adults in Singapore and Malaysia. A skin prick test (SPT) for common house dust mites was also conducted to determine the atopic (allergic) status. We identified 1,550 atopic dermatitis (AD), 1,301 allergic asthma (AS), and 3,757 allergic rhinitis (AR) atopic cases. We derived a novel dietary index, Diet Quality based on Total Fat Amount (DQTFA), to examine the association between eating patterns for estimated total fat amount with various atopic outcomes.

    RESULTS: There was a preponderance of subjects having positive SPT reaction (69.0%) with the prevalence of AR being the highest (32.7%), then AD (13.5%), and AS (11.3%). Additionally, there is a significantly higher proportion of subjects with an atopy background and atopic diseases consume diets with a high estimated mean fat amount. The adherence to a dietary pattern of the higher estimated total fat amount was shown to be strongly associated with all atopic diseases and exhibited dose-dependent responses in the univariate analysis. These associations remained significant even with the adjustments for age, gender, body mass index, use of alcohol, sedentary lifestyles, and physical activity. A dietary pattern for high-fat amount is more strongly associated with AS (adjusted odds ratio [AOR]: 1.524; 95% confidence interval [CI]: 1.216-1.725; p < 0.001) and AR (AOR: 1.294; 95% CI: 1.107-1.512; p < 0.001) compared to AD (AOR: 1.278; 95% CI: 1.049-1.559; p < 0.05). Finally, it was shown that having either one of the atopic comorbidities was strongly associated with a dietary pattern of high-fat amounts (AOR: 1.360; 95% CI: 1.161-1.594; p < 0.001).

    CONCLUSION: Our findings altogether provide initial evidence that the dietary pattern of a diet high in fat amount is associated with an increased risk of atopy and atopic diseases in young Chinese adults in Singapore and Malaysia. Balancing the consumption of dietary fats and changing personal dietary habits by choosing foods of the lower fat amount may reduce the associated odds of atopic diseases.

  2. Lim JJ, Reginald K, Say YH, Liu MH, Chew FT
    BMC Public Health, 2023 Sep 19;23(1):1818.
    PMID: 37726698 DOI: 10.1186/s12889-023-16736-y
    BACKGROUND: The prevalence of atopic dermatitis (AD) has been increasing in recent years, especially in Asia. There is growing evidence to suggest the importance of dietary patterns in the development and management of AD. Here, we seek to understand how certain dietary patterns in a Singapore/Malaysia population are associated with various risks of AD development and exacerbation.

    METHODS: A standardized questionnaire following the International Study of Asthma and Allergies in Childhood (ISAAC) guidelines was investigator-administered to a clinically and epidemiology well-defined allergic cohort of 13,561 young Chinese adults aged 19-22. Information on their sociodemographic, lifestyle, dietary habits, and personal and family medical atopic histories were obtained. Allergic sensitization was assessed by a skin prick test to mite allergens. Spearman's rank-order correlation was used to assess the correlation between the intake frequencies of 16 food types. Dietary patterns were identified using principal component analysis. Four corresponding dietary scores were derived to examine the association of identified dietary patterns with allergic sensitization and AD exacerbations through a multivariable logistic regression that controlled for age, gender, parental eczema, BMI, and lifestyle factors.

    RESULTS: The correlation is the strongest between the intake of butter and margarine (R = 0.65). We identified four dietary patterns, "high-calorie foods", "plant-based foods", "meat and rice", and "probiotics, milk and eggs", and these accounted for 47.4% of the variance in the dietary habits among the subjects. Among these patterns, moderate-to-high intake of "plant-based foods" conferred a negative association for chronic (Adjusted odds ratio (AOR): 0.706; 95% confidence interval (CI): 0.589-0.847; p 

  3. Tiew PY, Dicker AJ, Keir HR, Poh ME, Pang SL, Mac Aogáin M, et al.
    Eur Respir J, 2021 Mar;57(3).
    PMID: 32972986 DOI: 10.1183/13993003.02050-2020
    INTRODUCTION: The chronic obstructive pulmonary disease (COPD) bacteriome associates with disease severity, exacerbations and mortality. While COPD patients are susceptible to fungal sensitisation, the role of the fungal mycobiome remains uncertain.

    METHODS: We report the largest multicentre evaluation of the COPD airway mycobiome to date, including participants from Asia (Singapore and Malaysia) and the UK (Scotland) when stable (n=337) and during exacerbations (n=66) as well as nondiseased (healthy) controls (n=47). Longitudinal mycobiome analysis was performed during and following COPD exacerbations (n=34), and examined in terms of exacerbation frequency, 2-year mortality and occurrence of serum specific IgE (sIgE) against selected fungi.

    RESULTS: A distinct mycobiome profile is observed in COPD compared with controls as evidenced by increased α-diversity (Shannon index; p<0.001). Significant airway mycobiome differences, including greater interfungal interaction (by co-occurrence), characterise very frequent COPD exacerbators (three or more exacerbations per year) (permutational multivariate ANOVA; adjusted p<0.001). Longitudinal analyses during exacerbations and following treatment with antibiotics and corticosteroids did not reveal any significant change in airway mycobiome profile. Unsupervised clustering resulted in two clinically distinct COPD groups: one with increased symptoms (COPD Assessment Test score) and Saccharomyces dominance, and another with very frequent exacerbations and higher mortality characterised by Aspergillus, Curvularia and Penicillium with a concomitant increase in serum sIgE levels against the same fungi. During acute exacerbations of COPD, lower fungal diversity associates with higher 2-year mortality.

    CONCLUSION: The airway mycobiome in COPD is characterised by specific fungal genera associated with exacerbations and increased mortality.

  4. Teh CK, Lee HL, Abidin H, Ong AL, Mayes S, Chew FT, et al.
    BMC Plant Biol, 2019 Nov 05;19(1):470.
    PMID: 31690276 DOI: 10.1186/s12870-019-2062-x
    BACKGROUND: Legitimacy in breeding and commercial crop production depends on optimised protocols to ensure purity of crosses and correct field planting of material. In oil palm, the presence of three fruit forms permits these assumptions to be tested, although only after field planting. The presence of incorrect fruit forms in a cross is a clear sign of illegitimacy. Given that tenera forms produce 30% more oil for the same weight of fruit as dura, the presence of low levels of dura contamination can have major effect during the economic lifespan of an oil palm, which is around 25 years. We evaluated two methods for legitimacy test 1) The use of SHELL markers to the gene that determines the shell-thickness trait 2) The use of SNP markers, to determine the legitimacy of the cross.

    RESULTS: Our results indicate that the SHELL markers can theoretically reduce the major losses due to dura contamination of tenera planting material. However, these markers cannot distinguish illegitimate tenera, which reduces the value of having bred elite tenera for commercial planting and in the breeding programme, where fruit form is of limited utility, and incorrect identity could lead to significant problems. We propose an optimised approach using SNPs for routine quality control.

    CONCLUSIONS: Both dura and tenera contamination can be identified and removed at or before the nursery stage. An optimised legitimacy assay using SNP markers coupled with a suitable sampling scheme is now ready to be deployed as a standard control for seed production and breeding in oil palm. The same approach will also be an effective solution for other perennial crops, such as coconut and date palm.

  5. Lee BW, Yap HK, Chew FT, Quah TC, Prabhakaran K, Chan GS, et al.
    Cytometry, 1996 Mar 15;26(1):8-15.
    PMID: 8809475
    Flow cytometric analysis of lymphocyte subsets were evaluated in 391 healthy Asian subjects ranging in age from birth to 40 years. Lymphocyte subsets were analysed using specific monoclonal antibodies: CD20 (B cells), CD3 and CD2 (T cells), CD16 and CD56+ (NK cells), CD4/CD3+ (helper-inducer T cells), CD8/ CD3+ (suppressor/cytotoxic T cells), HLA-DR expression on CD3 and CD25 (Tac) on CD3. The total white cell count, absolute lymphocyte counts, and B cell percentages peaked in infancy and declined steadily with age. Absolute counts of each subset, which were derived from absolute lymphocyte counts, also followed this trend. Increases with age were seen in the NK, T cell (CD2, CD3), and CD8 percentages. Males tended to have higher NK and CD8 percentages than females, and, conversely, females had higher CD3 and CD4 percentages than males. Comparison of our results with studies involving Caucasian subjects indicated higher NK percentages in our Asian population and lower CD4 absolute counts in the males of our population. These results indicate the presence of age, sex, and probable racial differences in lymphocyte subset expression. Our results may serve as reference standards for the Asian population.
  6. Lim JJ, Lim YYE, Ng JY, Malipeddi P, Ng YT, Teo WY, et al.
    World Allergy Organ J, 2022 Dec;15(12):100722.
    PMID: 36438192 DOI: 10.1016/j.waojou.2022.100722
    BACKGROUND: Atopic Dermatitis (AD) is a highly pruritic, chronic-recurrent inflammatory skin condition associated with erythematous lesions that affect a significant proportion of the population. Although AD is a non-communicable disease, it can cause pain, unbearable itchiness, sleep disturbance, loss of work productivity, and reduced quality of life. As a heterogeneous disease, AD is influenced by multiple genes and environmental triggers. As such, it is imperative to gain a deeper insight into the intricate gene-environment relationship that results in the manifestation of AD.

    METHODS: There are 3 objectives in our study. We first aim to update the epidemiological status of AD amongst young adults in Singapore and Malaysia, in particular amongst the Chinese ethnic background. Next, we re-evaluated the possible associated risk factors, identified in our previous meta-analysis and review studies, on the current cohort. Finally, we described here a detailed disease presentation and symptoms profile of our Singapore and Malaysia Cross-Sectional Genetics Epidemiology Study (SMCGES) cohort, which forms the base population for the discovery of associated genetic factors in relation to asthma, allergic diseases and skin conditions. Based on a skin prick test (SPT) and investigator-administered medical history responses, we assessed the AD profiles of 11 494 participants and the significant modifiable and non-modifiable factors associated with disease presentation.

    RESULTS: The prevalence of AD in the combined population was 13.5%. Chronic and moderate/severe AD were observed in 35.5% and 40.5% of the individuals with AD, respectively. Family history of atopic diseases, prior history of drug allergies, a history of acne, increased household family monthly income, higher number of individuals in the shared household, parental education, sedentary lifestyle, physical activities, alcoholic consumption, and even quality of diet was significantly associated with AD presentation, chronicity, and severity. Among all the factors evaluated, family and personal history of atopic diseases imposed the strongest associated risk.

    CONCLUSIONS: These findings supported our previous review studies and affirmed that familial history or genetic factors critically influence the development of AD in our population and environment. Environmental and other modifiable factors can also trigger AD throughout the lifetime of individuals who have especially inherited the atopic disease disposition. A better understanding of how these risk factors affect AD individuals in our population can facilitate disease surveillance, monitor disease control, and serve as a description for our future genetic epidemiology studies.

  7. Wong QYA, Lim JJ, Ng JY, Malipeddi P, Lim YYE, Sio YY, et al.
    World Allergy Organ J, 2023 Mar;16(3):100757.
    PMID: 36968625 DOI: 10.1016/j.waojou.2023.100757
    BACKGROUND: Asthma is a chronic inflammatory disease of the airway characterized by respiratory symptoms: wheezing, shortness of breath, coughing, and chest tightness. Globally, asthma affects over 300 million individuals and carries high morbidity and mortality burden. Previous studies have estimated the prevalence of asthma; however, prevalence estimates have been changing over time. Here, in a population of young Chinese adults from Singapore, we aimed to obtain an updated prevalence of asthma and its phenotypes, and identify potential associated risk factors.

    METHODS: The Singapore/Malaysia Cross-Sectional Genetics Epidemiology Study (SMCGES) is an ongoing study which uses established ISAAC guidelines to collect epidemiological data and information pertaining to allergic diseases such as asthma. Responses from young Chinese adults recruited in the National University of Singapore were analyzed.

    RESULTS: Lifetime asthma prevalence rate was estimated at 19.1% (2049/10,736), while current asthma prevalence rate was estimated at 6.3% (679/10,736). For ever asthma, the most important risk factor was a parental history of asthma. Increased consumption of pulses (aOR: 0.822, 95% CI: 0.706-0.958) was associated with a lowered odds of ever asthma, but cereals (aOR: 1.256, 95% CI: 1.006-1.580), pasta (aOR: 1.265, 95% CI: 1.027-1.553), butter (aOR: 1.350, 95% CI: 1.113-1.632), and margarine (aOR: 1.343, 95% CI: 1.081-1.660) were associated with a higher risk of ever asthma. Increased television/computer usage was associated with a decreased risk of ever asthma (aOR: 0.448, 95% CI: 0.367-0.545). Conversely, genetic factors had a lower strength of effect on current asthma (parental history of asthma - OR: 1.465, 95% CI: 1.135-1.888) as compared to ever asthma. Only increased potato consumption was significantly associated with an increased risk of current asthma (most or all days per week vs never or only occasionally - aOR: 1.577, 95% CI: 1.145-2.180). Physical activity (aOR: 0.693, 95% CI: 0.542-0.885) was associated with a lower odds of asthma, while second-hand smoke exposure was associated with an increased risk for current asthma (aOR: 1.435, 95% CI: 1.001-2.047).

    CONCLUSION: Overall, the prevalence of lifetime asthma and current asthma among young Chinese adults was 19.1% and 6.3%, higher than that of previous studies. Our results suggested a stronger association between genetic factors and ever asthma as compared to current asthma. Parental asthma was the most important intrinsic epidemiological factor for asthma manifestation, while various foods, physical activity levels, and television or computer usage were also significantly associated with asthma. Future studies should consider risk factors in conjunction with other accompanying variables given the potential interactions between them, to discern the effects of environment and lifestyle on asthma more distinctly.

  8. Tan EC, Lee BW, Tay AW, Chew FT, Tay AH
    Allergy, 1999 Apr;54(4):402-3.
    PMID: 10371104
  9. Teo WY, Lim YYE, Sio YY, Say YH, Reginald K, Chew FT
    World Allergy Organ J, 2024 Feb;17(2):100869.
    PMID: 38298829 DOI: 10.1016/j.waojou.2023.100869
    BACKGROUND: Atopic dermatitis (AD) is a complex inflammatory disease with a strong genetic component. A singular approach of genome wide association studies (GWAS) can identify AD-associated genetic variants, but is unable to explain their functional relevance in AD. This study aims to characterize AD-associated genetic variants and elucidate the mechanisms leading to AD through a multi-omics approach.

    METHODS: GWAS identified an association between genetic variants at 6p21.32 locus and AD. Genotypes of 6p21.32 locus variants were evaluated against LOC100294145 expression in peripheral blood mononuclear cells (PBMCs). Their influence on LOC100294145 promoter activity was measured in vitro via a dual-luciferase assay. The function of LOC100294145 was then elucidated through a combination of co-expression analyses and gene enrichment with g:Profiler. Mendelian randomization was further used to assess the causal regulatory effect of LOC100294145 on its co-expressed genes.

    RESULTS: Minor alleles of rs116160149 and rs115388857 at 6p21.32 locus were associated with increased AD risk (p = 2.175 × 10-8, OR = 1.552; p = 2.805 × 10-9, OR = 1.55) and higher LOC100294145 expression in PBMCs (adjusted p = 0.182; 8.267 × 10-12). LOC100294145 expression was also found to be increased in those with AD (adjusted p = 3.653 × 10-2). The genotype effect of 6p21.32 locus on LOC100294145 promoter activity was further validated in vitro. Co-expression analyses predicted LOC100294145 protein's involvement in interleukin-27 and type 1 interferon signaling, which was further substantiated through mendelian randomization.

    CONCLUSION: Genetic variants at 6p21.32 locus increase AD susceptibility through raising LOC100294145 expression. A multi-omics approach enabled the deduction of its pathogenesis model comprising dysregulation of hub genes involved in type 1 interferon and interleukin 27 signaling.

  10. Reginald K, Pang SL, Chew FT
    Sci Rep, 2019 Aug 22;9(1):12239.
    PMID: 31439916 DOI: 10.1038/s41598-019-48688-y
    Blomia tropicalis has been recognized as a cause of allergic diseases in the tropical and subtropical regions. Here we report the immuno-characterization of its group 2 allergen, Blo t 2. Allergen Blo t 2 was amplified from the cDNA of B. tropicalis using degenerate primers, expressed in Escherichia coli as a recombinant protein and purified to homogeneity. The mature protein of Blo t 2 was 126 amino acids long with 52% sequence identity to Der p 2 and apparent molecular mass of 15 kDa. Circular dichroism spectroscopy showed that Blo t 2 is mainly a beta-sheeted protein. We confirmed the presence of three disulfide bonds in recombinant (r) Blo t 2 protein using electrospray mass spectrometry. Thirty-four percent of dust-mite allergic individuals from the Singapore showed specific IgE binding to rBlo t 2 as tested using immuno dot-blots. IgE-cross reactivity assays showed that Blo t 2 had between 20-50% of unique IgE-epitopes compared to Der p 2. IgE binding of native and recombinant forms of Blo t 2 were highly concordant (r2 = 0.77, p 
  11. Lim JJ, Lim YYE, Ng JY, Malipeddi P, Ng YT, Teo WY, et al.
    Dermatology, 2024;240(1):77-84.
    PMID: 37666213 DOI: 10.1159/000533942
    BACKGROUND: We see increasing evidence that dietary and nutrients factors play a pivotal role in allergic diseases and recent global findings suggest that dietary habits influence the pathogenesis of atopic dermatitis (AD). Frequent consumption of fast food diets is associated with AD development. Despite the rising prevalence of AD in Asia, efforts in investigating the role of dietary habits and AD in adults are still lacking.

    METHODS: We evaluated the association between the dietary intake of 16 food types and AD manifestations using our Singapore/Malaysia Cross-sectional Genetics Epidemiology Study (SMCGES) population. Dietary habits profiles of 11,494 young Chinese adults (1,550 AD cases/2,978 non-atopic controls/6,386 atopic controls) were assessed by an investigator-administered questionnaire. AD cases were further evaluated for their chronicity (550 chronic) and severity (628 moderate-to-severe). Additionally, we derived a novel food index, Quality of Diet based on Glycaemic Index Score (QDGIS), to examine the association between dietary intake of glycaemic index (GI) and various AD phenotypes.

    RESULTS: The majority of AD subjects are distributed in the good (37.1%) and moderate (36.2%) QDGIS classes. From the multivariable analyses for age and gender, a moderate QDGIS class was significantly associated with a lower odds of AD (adjusted odds ratio (AOR): 0.844; 95% confidence interval (CI): 0.719-0.991; p < 0.05) and moderate-to-severe AD (AOR: 0.839; 95% CI: 0.714-0.985; p < 0.05). A good QDGIS class was only significantly associated with a lower odds of chronic AD (AOR: 0.769; 95% CI: 0.606-0.976; p < 0.05). Among high GI foods, frequent consumption of burgers/fast food was strongly associated with an increased risk of chronic and moderate-to-severe AD. Among low GI foods, increased intake frequencies of fruits, vegetables, and pulses decreased the odds of AD. Finally, we identified significant associations between frequent seafood, margarine, butter, and pasta consumption with an increased odds of AD despite them having little GI values.

    CONCLUSION: While genetic components are well-established in their risks associated with increased AD prevalence, there is still a lack of a focus epidemiology study associating dietary influence with AD. Based on the first allergic epidemiology study conducted here in Singapore and Malaysia, it laid the groundwork to guide potential dietary interventions from changing personal dietary habits.

  12. Reginald K, Tan CL, Chen S, Yuen L, Goh SY, Chew FT
    Sci Rep, 2018 08 06;8(1):11743.
    PMID: 30082894 DOI: 10.1038/s41598-018-30224-z
    We previously identified an expressed sequence tag clone, Der f 22, showing 41% amino acid identity to published Der f 2, and show that both genes are possible paralogues. The objective of this study was to characterize the genomic, proteomic and immunological functions Der f 22 and Der f 2. The full-length sequence of Der f 2 and Der f 22 coded for mature proteins of 129 and 135 amino acids respectively, both containing 6 cysteine residues. Phylogenetic analysis of known group 2 allergens and their homologues from our expressed sequence tag library showed that Der f 22 is a paralogue of Der f 2. Both Der f 2 and Der f 22 were single gene products with one intron. Both allergens showed specific IgE-binding to over 40% of the atopic patients, with limited of cross-reactivity. Both allergens were detected at the gut region of D. farinae by immunostaining. Der f 22 is an important allergen with significant IgE reactivity among the atopic population, and should be considered in the diagnostic panel and evaluated as future hypoallergen vaccine therapeutic target.
  13. Teh CK, Muaz SD, Tangaya P, Fong PY, Ong AL, Mayes S, et al.
    Sci Rep, 2017 06 08;7(1):3118.
    PMID: 28596562 DOI: 10.1038/s41598-017-03225-7
    The fundamental trait in selective breeding of oil palm (Eleais guineensis Jacq.) is the shell thickness surrounding the kernel. The monogenic shell thickness is inversely correlated to mesocarp thickness, where the crude palm oil accumulates. Commercial thin-shelled tenera derived from thick-shelled dura × shell-less pisifera generally contain 30% higher oil per bunch. Two mutations, sh MPOB (M1) and sh AVROS (M2) in the SHELL gene - a type II MADS-box transcription factor mainly present in AVROS and Nigerian origins, were reported to be responsible for different fruit forms. In this study, we have tested 1,339 samples maintained in Sime Darby Plantation using both mutations. Five genotype-phenotype discrepancies and eight controls were then re-tested with all five reported mutations (sh AVROS , sh MPOB , sh MPOB2 , sh MPOB3 and sh MPOB4 ) within the same gene. The integration of genotypic data, pedigree records and shell formation model further explained the haploinsufficiency effect on the SHELL gene with different number of functional copies. Some rare mutations were also identified, suggesting a need to further confirm the existence of cis-compound mutations in the gene. With this, the prediction accuracy of fruit forms can be further improved, especially in introgressive hybrids of oil palm. Understanding causative variant segregation is extremely important, even for monogenic traits such as shell thickness in oil palm.
  14. Pang SL, Ho KL, Waterman J, Teh AH, Chew FT, Ng CL
    Acta Crystallogr F Struct Biol Commun, 2015 Nov;71(Pt 11):1396-400.
    PMID: 26527267 DOI: 10.1107/S2053230X1501818X
    Dermatophagoides farinae is one of the major house dust mite (HDM) species that cause allergic diseases. N-terminally His-tagged recombinant Der f 21 (rDer f 21), a group 21 allergen, with the signal peptide truncated was successfully overexpressed in an Escherichia coli expression system. The purified rDer f 21 protein was initially crystallized using the sitting-drop vapour-diffusion method. Well diffracting protein crystals were obtained after optimization of the crystallization conditions using the hanging-drop vapour-diffusion method with a reservoir solution consisting of 0.19 M Tris-HCl pH 8.0, 32% PEG 400 at 293 K. X-ray diffraction data were collected to 1.49 Å resolution using an in-house X-ray source. The crystal belonged to the C-centered monoclinic space group C2, with unit-cell parameters a = 123.46, b = 27.71, c = 90.25 Å, β = 125.84°. The calculated Matthews coefficient (VM) of 2.06 Å(3) Da(-1) suggests that there are two molecules per asymmetric unit, with a solvent content of 40.3%. Despite sharing high sequence identity with Blo t 5 (45%) and Blo t 21 (41%), both of which were determined to be monomeric in solution, size-exclusion chromatography, static light scattering and self-rotation function analysis indicate that rDer f 21 is likely to be a dimeric protein.
  15. Ng JY, Chew FT
    Skin Res Technol, 2024 Feb;30(2):e13620.
    PMID: 38376131 DOI: 10.1111/srt.13620
    BACKGROUND: We evaluate skin sagging phenotypes (eyebags, droopy eyelids, low eyebrow positioning) using written descriptive scales and photo-numeric scales. We also study how anti-ageing interventions and digital screen time influence skin sagging.

    AIM: We compare the two phenotype assessment methods with each other.

    METHOD: Skin sagging and personal lifestyle data obtained from 2885 ethnic Chinese young adults from the Singapore/Malaysia cross-sectional genetics epidemiology study (SMCGES) cohort were collated and compared.

    RESULTS: Significant correlations (p-value 

  16. Reginald K, Chew FT
    Sci Rep, 2018 02 21;8(1):3391.
    PMID: 29467434 DOI: 10.1038/s41598-018-21792-1
    Epitope mapping of Der p 2, a clinically important dust-mite allergen is the first step in designing immunotherapy hypoallergen vaccine candidates. Twenty-one single alanine mutants of Der p 2 were generated and their secondary structure was analysed using circular dichroism spectra. Only one mutant, K96A resulted in a misfolded protein. All mutants were tested for serum IgE reactivity using serum from dust mite allergic individuals by immuno dot-blots. Mutations to five residues, N10, E25, K77, K96 and E102 consistently showed reduced IgE reactions compared to wild-type Der p 2, and therefore these residues constitute the major IgE epitopes of Der p 2. Two mutants with consistent low IgE binding, K96A and E102A, were subsequently evaluated as hypoallergen candidates. IgG antibodies raised in mice against both mutants could inhibit human IgE-binding to WT Der p 2. Both mutants had intact T-cell epitopes as they were able to stimulate peripheral blood mononuclear cell proliferation similar to WT Der p 2. However, a switch in Th1:Th2 cytokine profile was not observed. In summary, we have identified the major conformational epitopes of Der p 2, and evaluated two Der p 2 hypoallergen vaccine candidates for immunotherapy.
  17. Pang SL, Ho KL, Waterman J, Rambo RP, Teh AH, Mathavan I, et al.
    Sci Rep, 2019 Mar 20;9(1):4933.
    PMID: 30894561 DOI: 10.1038/s41598-019-40879-x
    Group 21 and 5 allergens are homologous house dust mite proteins known as mid-tier allergens. To reveal the biological function of group 21 allergens and to understand better the allergenicity of the rDer f 21 allergen, we determined the 1.5 Å crystal structure of rDer f 21 allergen from Dermatophagoides farinae. The rDer f 21 protein consists of a three helical bundle, similar to available structures of group 21 and homologous group 5 allergens. The rDer f 21 dimer forms a hydrophobic binding pocket similar to the one in the Der p 5 allergen, which indicates that both of the homologous groups could share a similar function. By performing structure-guided mutagenesis, we mutated all 38 surface-exposed polar residues of the rDer f 21 allergen and carried out immuno-dot blot assays using 24 atopic sera. Six residues, K10, K26, K42, E43, K46, and K48, which are located in the region between the N-terminus and the loop 1 of rDer f 21 were identified as the major IgE epitopes of rDer f 21. Epitope mapping of all potential IgE epitopes on the surface of the rDer f 21 crystal structure revealed heterogeneity in the sIgE recognition of the allergen epitopes in atopic individuals. The higher the allergen-sIgE level of an individual, the higher the number of epitope residues that are found in the allergen. The results illustrate the clear correlation between the number of specific major epitope residues in an allergen and the sIgE level of the atopic population.
  18. Reginald K, Chew FT
    Mol Immunol, 2023 Sep;161:11-24.
    PMID: 37480600 DOI: 10.1016/j.molimm.2023.07.004
    PURPOSE OF REVIEW: This review evaluates the current modes of allergen-specific immunotherapy for cockroach allergens, in terms of clinical outcomes and explores future trends in the research and development needed for a more targeted cockroach immunotherapy approach with the best efficacy and minimum adverse effects.

    SUMMARY: Cockroach allergy is an important risk factor for allergic rhinitis in the tropics, that disproportionately affects children and young adults and those living in poor socio-economic environments. Immunotherapy would provide long-lasting improvement in quality of life, with reduced medication intake. However, the present treatment regime is long and has a risk of adverse effects. In addition, cockroach does not seem to have an immuno-dominant allergen, that has been traditionally used to treat allergies from other sources. Future trends of cockroach immunotherapy involve precision diagnosis, to correctly identify the offending allergen. Next, precision immunotherapy with standardized allergens, which have been processed in a way that maintains an immunological response without allergic reactions. This approach can be coupled with modern adjuvants and delivery systems that promote a Th1/Treg environment, thereby modulating the immune response away from the allergenic response.

  19. Kwong QB, Teh CK, Ong AL, Heng HY, Lee HL, Mohamed M, et al.
    Mol Plant, 2016 Aug 01;9(8):1132-1141.
    PMID: 27112659 DOI: 10.1016/j.molp.2016.04.010
    High-density single nucleotide polymorphism (SNP) genotyping arrays are powerful tools that can measure the level of genetic polymorphism within a population. To develop a whole-genome SNP array for oil palms, SNP discovery was performed using deep resequencing of eight libraries derived from 132 Elaeis guineensis and Elaeis oleifera palms belonging to 59 origins, resulting in the discovery of >3 million putative SNPs. After SNP filtering, the Illumina OP200K custom array was built with 170 860 successful probes. Phenetic clustering analysis revealed that the array could distinguish between palms of different origins in a way consistent with pedigree records. Genome-wide linkage disequilibrium declined more slowly for the commercial populations (ranging from 120 kb at r(2) = 0.43 to 146 kb at r(2) = 0.50) when compared with the semi-wild populations (19.5 kb at r(2) = 0.22). Genetic fixation mapping comparing the semi-wild and commercial population identified 321 selective sweeps. A genome-wide association study (GWAS) detected a significant peak on chromosome 2 associated with the polygenic component of the shell thickness trait (based on the trait shell-to-fruit; S/F %) in tenera palms. Testing of a genomic selection model on the same trait resulted in good prediction accuracy (r = 0.65) with 42% of the S/F % variation explained. The first high-density SNP genotyping array for oil palm has been developed and shown to be robust for use in genetic studies and with potential for developing early trait prediction to shorten the oil palm breeding cycle.
  20. Lim JJ, Reginald K, Say YH, Liu MH, Chew FT
    JID Innov, 2023 Nov;3(6):100224.
    PMID: 37731471 DOI: 10.1016/j.xjidi.2023.100224
    Through an investigator-administered questionnaire that follows the standard protocol of the International Study of Allergy and Asthma in Childhood, data on symptomatic histories of eczema and dietary habits were collected from 11,494 young Chinese adults in Singapore/Malaysia. Allergic sensitization status was assessed through a skin prick test reactivity to common house dust mites. Using three dietary indices (dietary protein score, animal protein score, and plant protein score), the associations between atopic dermatitis, intrinsic eczema, allergic sensitization, and intake of various proteins were estimated. On average, most subjects frequently eat meat, vegetables, and rice in their diets. Through a multivariable logistic regression adjusted for age, sex, body mass index, and parental eczema, subjects with high dietary protein score (adjusted OR = 1.397; 95% confidence interval = 1.133-1.724; P < 0.003) and high animal protein score (adjusted OR = 1.353; 95% confidence interval = 1.106-1.682; P < 0.003) were associated with increased risk of atopic dermatitis. Interestingly, synergy factor analysis revealed that a higher intake of plant proteins than animal proteins in diets significantly reduced overall associated risks of atopic dermatitis and allergic sensitization but not those of intrinsic eczema. Most importantly, these associations are independent of dietary fat intake. Taken together, frequent adherence to diets rich in plant proteins reduced associated risks of atopic dermatitis in Singapore/Malaysia Chinese adults.
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