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Allergic Asthma in Singapore Chinese - Epidemiology and Genetics.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Allergic Asthma in Singapore Chinese - Epidemiology and Genetics./
作者:	Yie, Sio Yang.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2020,
面頁冊數:	786 p.
附註:	Source: Dissertations Abstracts International, Volume: 84-04, Section: B.
Contained By:	Dissertations Abstracts International84-04B.
標題:	Young adults. -
電子資源:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=29353108
ISBN:	9798352687116

Allergic Asthma in Singapore Chinese - Epidemiology and Genetics.
Yie, Sio Yang.

Allergic Asthma in Singapore Chinese - Epidemiology and Genetics. - Ann Arbor : ProQuest Dissertations & Theses, 2020 - 786 p.

Source: Dissertations Abstracts International, Volume: 84-04, Section: B.

Thesis (Ph.D.)--National University of Singapore (Singapore), 2020.

This item must not be sold to any third party vendors.

Asthma is a complex respiratory syndrome characterized by chronic inflammation in the lower airways. This disease has become a major health issue, with more than 300 million individuals affected worldwide. An increasing trend of asthma prevalence was observed in the western countries during the 1960s to 1990s period, while a plateauing pattern was found from the last decade of the 20th century until the present. As multiple Asia-Pacific countries advancing through the trend of industrialization, the prevalence of asthma and asthma-related symptoms in this region were also increased during the period of 1998 to 2007. In the Asian population, the most replicated asthma risk factor was the family medical history of asthma, showing an overall odds ratio of 4.87 (95% CI: 3.91- 6.06) based on the findings from 27 studies. This suggests a high heritability of this disease (Chapter 1). In Singapore, the lifetime prevalence of asthma had been rising from 3.4-5.5% in the year of 1972, up until 16.3-27.4% in the year of 2001. During the period of 2005 to 2018, this current study has shown the lifetime prevalence of allergic asthma to be 15% in the Singapore Chinese population, with 18.5% of these asthma-affected individuals having persisted symptoms until adulthood (Chapter 2). Gender, number of years staying in Singapore, type of housing, total family income and body mass index were all identified as the risk factors of allergic asthma in the current study population. Nevertheless, the parental history of allergic diseases, including asthma, hay fever, and eczema, was still found to be the strongest risk factor contributing to asthma susceptibility (Chapter 2). This indicates a significant proportion of the inter-individual difference in disease susceptibility can be attributed to genetic factors. To provide a better understanding of the genetic basis of asthma pathogenesis, we first characterized 2 asthma candidate genes, namely PER1-like domain-containing protein 1 (PERLD1) and Erb-B2 Receptor Tyrosine Kinase 2 (ERBB2) that were both identified from a prior asthma pooled-genome wide association study (GWAS) conducted on the Singapore Chinese population. The genetic variants from these genes were shown to associate with the immune cell proliferation (PERLD1) and the mitogen-activated protein kinase (MAPK) signaling pathway (ERBB2) that were both involved in the airway inflammatory response (Chapter 3). We also investigated the association of 60 highly replicated asthma candidate genes with asthma risk in our study population. Of these, genetic variants in the ORM1-like protein 3 (ORMDL3) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) genes were directly associated with the disease and demonstrated functional relevance to asthma development (Chapter 4). The epistatic interaction between the phenylethanolamine N-methyltransferase (PNMT) and β2-adrenergic receptor (ADRB2) genes was found associated with asthma in the Singapore Chinese population and involved in regulating the serum level of epinephrine (Chapter 5). Lastly, we conducted a GWAS on the Singapore Chinese population and performed a genetic risk prediction using these whole-genome data to provide an overall estimation of the genetic contribution to the development of asthma (Chapter 6). Overall, the current study has identified environmental, genetic, and host-related factors that were associated with asthma in the Singapore Chinese population. Functional characterizations of multiple asthma-associated genes can also improve the current understanding of the genetic basis of asthma development. Collectively, these findings provide opportunities for the development of better asthma diagnostic, management, and therapeutic approaches.

ISBN: 9798352687116Subjects--Topical Terms:

598212
Young adults.

Allergic Asthma in Singapore Chinese - Epidemiology and Genetics.
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520 $a Asthma is a complex respiratory syndrome characterized by chronic inflammation in the lower airways. This disease has become a major health issue, with more than 300 million individuals affected worldwide. An increasing trend of asthma prevalence was observed in the western countries during the 1960s to 1990s period, while a plateauing pattern was found from the last decade of the 20th century until the present. As multiple Asia-Pacific countries advancing through the trend of industrialization, the prevalence of asthma and asthma-related symptoms in this region were also increased during the period of 1998 to 2007. In the Asian population, the most replicated asthma risk factor was the family medical history of asthma, showing an overall odds ratio of 4.87 (95% CI: 3.91- 6.06) based on the findings from 27 studies. This suggests a high heritability of this disease (Chapter 1). In Singapore, the lifetime prevalence of asthma had been rising from 3.4-5.5% in the year of 1972, up until 16.3-27.4% in the year of 2001. During the period of 2005 to 2018, this current study has shown the lifetime prevalence of allergic asthma to be 15% in the Singapore Chinese population, with 18.5% of these asthma-affected individuals having persisted symptoms until adulthood (Chapter 2). Gender, number of years staying in Singapore, type of housing, total family income and body mass index were all identified as the risk factors of allergic asthma in the current study population. Nevertheless, the parental history of allergic diseases, including asthma, hay fever, and eczema, was still found to be the strongest risk factor contributing to asthma susceptibility (Chapter 2). This indicates a significant proportion of the inter-individual difference in disease susceptibility can be attributed to genetic factors. To provide a better understanding of the genetic basis of asthma pathogenesis, we first characterized 2 asthma candidate genes, namely PER1-like domain-containing protein 1 (PERLD1) and Erb-B2 Receptor Tyrosine Kinase 2 (ERBB2) that were both identified from a prior asthma pooled-genome wide association study (GWAS) conducted on the Singapore Chinese population. The genetic variants from these genes were shown to associate with the immune cell proliferation (PERLD1) and the mitogen-activated protein kinase (MAPK) signaling pathway (ERBB2) that were both involved in the airway inflammatory response (Chapter 3). We also investigated the association of 60 highly replicated asthma candidate genes with asthma risk in our study population. Of these, genetic variants in the ORM1-like protein 3 (ORMDL3) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) genes were directly associated with the disease and demonstrated functional relevance to asthma development (Chapter 4). The epistatic interaction between the phenylethanolamine N-methyltransferase (PNMT) and β2-adrenergic receptor (ADRB2) genes was found associated with asthma in the Singapore Chinese population and involved in regulating the serum level of epinephrine (Chapter 5). Lastly, we conducted a GWAS on the Singapore Chinese population and performed a genetic risk prediction using these whole-genome data to provide an overall estimation of the genetic contribution to the development of asthma (Chapter 6). Overall, the current study has identified environmental, genetic, and host-related factors that were associated with asthma in the Singapore Chinese population. Functional characterizations of multiple asthma-associated genes can also improve the current understanding of the genetic basis of asthma development. Collectively, these findings provide opportunities for the development of better asthma diagnostic, management, and therapeutic approaches.
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