Genetic Association With Various Severities, Phenotypes and Endotypes of Asthma.

Currently, many studies on asthma genetics are limited by the dominance of populations of European descent. In addition, there are few genetic studies that focus on moderate-to-severe asthma.

There is limited information on genetics associated with asthma in Chinese. An earlier meta-analysis found that ADAM33, FcεRIb, RANTES, TNF-a, ACE, b2-AR, IL-4R and IL-13 genes could be proposed as asthma susceptible genes in the Chinese population. However, given the limited number of studies, more data are required to validate these associations.

Future research must address key issues such as the broad clinical variability of asthma and the underrepresentation of populations of non-European heritage. Endotype-specific SNPs and unique biological insights may be obtained by conducting GWAS/EWAS on homogeneous populations of more therapy-resistant T2-low, adult-onset, obesity-associated asthma or asthma with particular co-morbidities.

Objectives Primary objective To investigate the association between genetic polymorphisms and various severities of asthma (e.g. mild, moderate, severe).

Secondary objectives

• Identify the most common genetic variants associated with asthma in Chinese patients.
• Determine the frequency and distribution of these genetic variants in Chinese patients compared to healthy controls.
• Explore the potential interactions between genetic and environmental factors in the development of asthma in Chinese patients.
• Explore the frequency and distribution of these genetic variants in patients with various phenotypes and endotypes (examples: including TH2 high asthma, Asthma COPD overlap, poor lung function, onset of illness)

This is a prospective observational study in outpatients with asthma seen and treated by physicians in the Prince of Wales Hospital. A total of 1000 asthma patients will be enrolled, along with 1000 controls matched for age, sex, and ethnicity. All participants will provide blood samples for genetic analysis, and clinical data will be collected from medical records and patient interviews. Genetic variants will be genotyped using high-throughput sequencing methods.

Inclusion criteria

• • All patients with confirmed diagnosis of asthma (defined as those with a consistent history and prior documented evidence of variable airflow obstruction, with evidence of an increase in FEV1 greater than 12% or 400 mL following bronchodilator or bronchial hyperresponsiveness on bronchial provocation testing, when stable) 12

• Able to sign written informed consent form to participate in the study.

Exclusion criteria

• • Patients currently with acute exacerbation of asthma by GINA guideline. (For subjects with asthma exacerbation, they can join the study after 6 weeks post recovery from the exacerbation.)

• Patients with respiratory diseases that can show similar symptoms to chronic airway diseases such as bronchiectasis, tuberculosis(TB)-destroyed lung parenchyma, endobronchial TB, and lung cancer, or those who have history of these diseases based on physician's judgment.
• Patients currently diagnosed with pneumonia and acute bronchitis.

For control subject: the inclusion will be having no clinical diagnosis of asthma.