Yee How Say

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    Modifiable and non-modifiable epidemiological risk factors for acne, acne severity and acne scarring among Malaysian Chinese: a cross-sectional study
    (BMC, 2021-03-27) Say, Yee-How; Heng, Anna Hwee Sing; Reginald, Kavita; Wong, Yi Ru; Teh, Keng Foo; Rawanan Shah, Smyrna Moti; Sio, Yang Yie; Ng, Yu Ting; Matta, Sri Anusha; Pang, Sze Lei; Chew, Fook Tim; Assoc Prof Fook Tim Chew; BIOLOGICAL SCIENCES; DEAN'S OFFICE (SCIENCE)
    Background: Acne vulgaris, a highly prevalent multifactorial inflammatory skin disease, can be categorised into different severity and scarring grades based on the type, number, and severity of lesions. While many epidemiology studies have investigated the risk factors for acne presentation, fewer studies have specifically studied the risk factors for acne severity and scarring. Therefore, this study investigated the prevalence of acne, acne severity and scarring grades, and their associated non-modifiable and modifiable epidemiological risk factors among Malaysian Chinese. Methods: A total of 1840 subjects (1117 cases/723 controls) completed an investigator-administered questionnaire as part of a cross-sectional study, which include socio-demographics, familial history, lifestyle factors, dietary habits, and acne history. Acne cases were further evaluated for their severity (n = 1051) and scarring (n = 1052) grades by a trained personnel. Results: Majority of the acne cases (up to 69%) had mild acne or Grade 1/2 scarring, while 21.6% had moderate/severe acne and 5.5% had Grade 3/4 scarring. Males had significantly higher risk of presenting with higher grades of acne scarring. Those who had acne, regardless of severity and scarring grades, had strong positive familial history (either in parents and/or sibling). Frequent consumption (most or all days) of foods that are commonly consumed during breakfast (butter, probiotic drinks, cereals and milk) decreased the risk for acne presentation and higher acne scarring, while periodic consumption (once/twice per week) of nuts and burgers/fast food decreased the risk for higher acne severity. Alcohol drinking was significantly associated with increased risk for acne presentation, while paternal, parental and household smoking were associated with reduced risk of more severe acne. Conclusions: In conclusion, positive familial history is a strong predisposing factor in influencing acne presentation, severity and scarring. Frequent consumption of foods that are commonly consumed during breakfast is protective against acne presentation.
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    Gene variants associated with acne vulgaris presentation and severity: a systematic review and meta-analysis
    (BMC, 2021-04-13) Heng, Anna Hwee Sing; Say, Yee-How; Sio, Yang Yie; Ng, Yu Ting; Chew, Fook Tim; Assoc Prof Fook Tim Chew; BIOLOGICAL SCIENCES; DEAN'S OFFICE (SCIENCE)
    Background: Multiple factors have been attributed to acne vulgaris predisposition and individual variations in the severity of skin symptoms, and genetics stood out as one of the major factors. Methods: We performed a systematic review on the genes and their variants that have been investigated for association with acne presentation and severity. A random-effect meta-analysis using the allele model (minor allele vs. major allele) was also conducted to provide an overall estimation of risk effects of frequently reported gene variants. This included a subset data of 982 acne cases and 846 controls extracted from our existing GWAS database on various allergic and skin diseases among Singapore Chinese. Results: Systematic review of 51 articles covering Asians and Caucasians found 60 genes/loci and their 100 variants implicated in acne; majority of them were in the intron, coding region/missense, and promoter regions. The commonly studied candidate genes/gene families include tumor necrosis factor (TNF), and the interleukin (IL) and cytochrome P450 (CYP) gene families. Our meta-analysis showed that most of the analyzed gene variants exhibited insignificant pooled odds ratio (pOR) and significant heterogeneity between studies. Nevertheless, we found that TNF rs1800629 A allele carriers and CYP17A1 rs743572 T allele carriers had significantly reduced mild acne risk [pOR: 0.60; 95% Confidence Interval (CI): 0.33–0.86] and severe acne risk (pOR: 0.59; 95% CI: 0.40–0.79), respectively, across populations. Overall, FST (follistatin) rs629725 A allele poses a significantly modest increased risk for acne presentation (pOR: 1.19, 95% CI: 1.14, 1.23), but neither TIMP2 (TIMP metallopeptidase inhibitor 2) rs8179090 nor CYP1A1 rs4646903 (pOR: 0.96, 95% CI: 0.80–1.12; pOR: 0.95, 95% CI: 0.83, 1.08), respectively. We discovered 15 novel SNPs in the 3′ UTR region of the Toll-like Receptor 4 gene (TLR4) associated with acne presentation. Conclusions: This systematic review and meta-analysis suggest that genes influencing inflammatory responses, specifically TNF, and genes influencing the function and activity of sebaceous glands, specifically CYP17A1 and FST, have potential risk variants for acne presentation and severity across populations. Understanding the genetic susceptibility factors and biological pathways involved in the pathogenesis of acne will help us to gain insights into developing effective acne treatments.
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    The ERBB2 Exonic Variant Pro1170Ala Modulates Mitogen-Activated Protein Kinase Signaling Cascades and Associates with Allergic Asthma
    (S. Karger AG, 2023-06-19) Sio, Yang Yie; Gan, Wei Liang; Ng, Wing Shan; Matta, Sri Anusha; Say, Yee-How; Teh, Keng Foo; Wong, Yi Ru; Rawanan Shah, Smyrna Moti; Reginald, Kavita; Chew, Fook Tim; BIOLOGICAL SCIENCES; DEAN'S OFFICE (SCIENCE)
    Introduction: Previous studies have indicated the ERBB2 genetic variants in the 17q12 locus might be associated with asthma; however, the functional effects of these variants on asthma risk remain inconclusive. This study aimed to characterize the functional roles of asthma-associated ERBB2 single nucleotide polymorphisms (SNPs) in asthma pathogenesis by performing genetic association and functional analysis studies. Methods: This study belongs to a part of an ongoing Singapore/Malaysia cross-sectional genetics and epidemiological study (SMCSGES). Genotype-phenotype associations were assessed by performing a genotyping assay on n = 4,348 ethnic Chinese individuals from the SMCSGES cohort. The phosphorylation levels of receptors and signaling proteins in the MAPK signaling cascades, including ErbB2, EGFR, and ERK1/2, were compared across the genotypes of asthma-associated SNPs through in vitro and ex vivo approaches. Results: The ERBB2 tag-SNP rs1058808 was significantly associated with allergic asthma, with the allele “G” identified as protective against the disease (adjusted logistic p = 6.56 × 10?9, OR = 0.625, 95% CI: 0.544–0.718). The allele “G” of rs1058808 resulted in a Pro1170Ala mutation that results in lower phosphorylation levels of ErbB2 in HaCat cells (p < 0.001), whereas the overall ERBB2 mRNA expression and the phosphorylation levels of EGFR remained unaffected. In the SMCSGES cohort, individuals carrying the genotype “GG” of rs1058808 had lower phosphorylated ERK1/2 proteins in the MAPK signaling cascade. A lower phosphorylation level of ERK1/2 was also associated with reduced asthma risk. Conclusions: The present findings highlighted the involvement of a functional exonic variant of ERBB2 in asthma development via modulating the MAPK signaling cascade.
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    Sensitization to Airborne Fungal Allergens Associates with Asthma and Allergic Rhinitis Presentation and Severity in the Singaporean/Malaysian Population
    (SPRINGER, 2021-07-13) Sio, Yang Yie; Pang, Sze Lei; Say, Yee-How; Teh, Keng Foo; Wong, Yi Ru; Shah, Smyrna Moti Rawanan; Reginald, Kavita; Chew, Fook Tim; Assoc Prof Fook Tim Chew; BIOLOGICAL SCIENCES; DEAN'S OFFICE (SCIENCE)
    Fungal spores and conidia are the major components of total airspora in the tropical Asia environment, and their sensitization patterns are often associated with allergic diseases such as asthma, allergic rhinitis (AR), and atopic dermatitis. Hence, we recruited a cross-sectional cohort of 9223 Singapore/Malaysia Chinese adults and assessed their sensitization against Curvularia lunata allergen using the skin prick test approach. A subset of this cohort (n = 254) was also screened for specific Immunoglobulin E (sIgE) titers against a panel of 11 fungal allergens. We found significant association of Curvularia lunata sensitization with the risk of asthma (OR = 1.66, 95% CI: 1.17–2.33; p = 0.00391) and AR (OR = 1.69, 95% CI: 1.18–2.41; p = 0.00396). Among asthmatic patients (n = 1680), Curvularia lunata sensitization also increased frequencies of wheezing symptoms (OR = 1.81, 95% CI: 1.05–2.96; p = 0.0239), general practitioner/specialist visits (OR = 2.37, 95% CI: 1.13–4.61; p = 0.0157), and other asthma-related exacerbation events (OR = 2.14, 95% CI: 1.04–4.10; p = 0.0289). In our serum cohort, sensitization to Aspergillus spp. was the most common fungal sensitization, with 23.6% (n = 60) had a class 3 and above sensitization (positive sensitization; sIgE titers of > 3.5 kU/L) against this allergen. Increasing sIgE titer against Aspergillus spp. was also correlated with increased AR risk and AR-related symptoms. In conclusion, our findings emphasize an important role of fungal sensitization in the manifestations of asthma and AR in the Southeast Asian Chinese population.
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    A Dietary Pattern for High Estimated Total Fat Amount Is Associated with Enhanced Allergy Sensitization and Atopic Diseases among Singapore/Malaysia Young Chinese Adults
    (S. Karger AG, 2023-06-30) Lim, Jun Jie; Reginald, Kavita; Say, Yee-How; Liu, Mei Hui; Chew, Fook Tim; BIOLOGICAL SCIENCES; DEAN'S OFFICE (SCIENCE)
    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.
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    Epidemiological Risk Factors Associated with Acne Vulgaris Presentation, Severity, and Scarring in a Singapore Chinese Population: A Cross-Sectional Study
    (S. Karger AG, 2021-06-01) Heng, Anna Hwee Sing; Say, Yee-How; Sio, Yang Yie; Ng, Yu Ting; Chew, Fook Tim; BIOLOGICAL SCIENCES; DEAN'S OFFICE (SCIENCE)
    Background: Acne vulgaris is classified based on the severity of skin lesions and post-healing scar types of these lesions. Numerous epidemiology studies have investigated the risk factors associated with acne presentation and severity, but studies for acne scarring are lacking. Objective: To investigate the prevalence of acne, severity, and scarring grades and their associated risk factors among Singapore Chinese. Methods: A total of 3,888 subjects (2,090 cases/1,798 controls; median age = 21 ± 4.589; range 17–71) completed an investigator-administered questionnaire as part of a cross-sectional study, which included sociodemographics, familial medical history, lifestyle factors, dietary habits, and acne history. Acne cases were further evaluated for their severity (n = 991) and scarring (n = 988) grades by a trained personnel. Results: The majority of the acne cases had mild acne/grade 1 scarring, while less than 1% had severe acne/grade 4 scarring. Parental acne was significantly associated with acne presentation and moderate/severe acne, while sibling acne was significantly associated with grade 3/4 scarring. Gender and age affected acne severity and scarring but not acne presentation, while tertiary maternal education level and the possession of ?3 siblings were particularly associated with acne scarring. Underweight BMI was protective against acne presentation, while atopic diseases (asthma, allergic rhinitis, eczema) were its predisposing factors. Of the evaluated lifestyle factors, computer/TV usage had significant association with acne presentation, while alcohol consumption was significantly associated with acne severity. Frequent milk consumption was associated with a protective effect for moderate-severe acne, while frequent butter consumption had a detrimental effect on acne scarring extent. Conclusion: Positive familial history is a strong predisposing factor in determining acne presentation, severity, and scarring. Demographic factors (gender, age) and sedentary lifestyle (increased computer/TV usage) influence acne presentation, while dietary habits (milk and butter consumption) influence acne severity and scarring. The predisposing factors revealed in this study could help us to gain insights into acne pathophysiology and hence develop interventions especially targeting modifiable risk factors.