Genetic Susceptibility

Genetic Susceptibility to Lung Diseases

Many lung conditions may arise not only due to environmental triggers but also because of inherited genetic factors. At Dr. Mutha Hospital, our experienced pulmonologists recognize the role of genetics in respiratory diseases and provide early diagnostic support and personalized treatment options.

What Is Genetic Susceptibility?

Every human shares over 99% of their DNA, yet millions of genetic differences can exist between individuals. Some of these differences may influence your susceptibility to diseases — including lung-related illnesses. This is known as genetic susceptibility.

Some lung conditions are entirely caused by genetic mutations (monogenic diseases), while others result from complex interactions between genes and external environmental factors (complex diseases).

Monogenic Lung Diseases (Single-Gene Disorders)

These conditions are directly caused by mutations in a specific gene and are typically inherited in a predictable pattern.

1. Cystic Fibrosis (CF)

CF is a recessive inherited disorder caused by mutations in the CFTR gene. It affects the regulation of salt and water in the lungs, gut, and skin. Over 1,000 mutations of this gene have been identified.

• Symptoms: Persistent lung infections, digestive issues, and thick mucus build-up

• Treatment: Targeted therapies like Ivacaftor help correct specific gene mutations (e.g., G551D)

2. Alpha-1 Antitrypsin Deficiency

Caused by mutations in the SERPINA1 gene, this condition leads to low levels of a protective lung protein. It’s more dangerous for smokers and may result in early-onset emphysema.

• Affects 1 in 2,000–5,000 people in Europe

• Strongly linked to early COPD development

3. Primary Ciliary Dyskinesia (PCD)

A rare inherited condition caused by gene mutations (e.g., DNAI1, DNAH5) affecting the function of cilia in the respiratory tract. It leads to mucus build-up and frequent infections.

Complex Genetic Lung Diseases

These conditions are influenced by both genetic factors and environmental exposures, such as pollution, allergens, smoking, or infections.

1. Asthma

Asthma is one of the most common complex lung diseases. Several genes may increase a person’s risk of developing asthma or allergic sensitivities.

• Genes such as IL-4, IL-13, ADAM33, and ORMDL3 have been associated with asthma

• Environmental triggers often interact with these genes to cause flare-ups

2. Chronic Obstructive Pulmonary Disease (COPD)

Although smoking is the main cause of COPD, only about 20% of smokers develop it, indicating a genetic influence.

• Susceptibility genes include TNFα, TGFβ1, GSTM1, and SOD3

• FAM13A, HHIP, and CHRNA3/CHRNA5 are associated loci identified in genome-wide studies

Several genes like ADAM33, MMP12, and TGFβ1 have been linked to both asthma and COPD, suggesting overlapping mechanisms.

Genetic Links in Other Lung Conditions

1. Pulmonary Fibrosis

While most cases are idiopathic, around 2% have hereditary links. Susceptible genes include:

• TERT

• TERC

• MUC5B

2. Sarcoidosis

Sarcoidosis is believed to result from both genetic and environmental factors. Genes involved include:

• HLA-DRB1

• ANXA11

• SS2

3. Lung Infections & Immunodeficiencies

Certain genetic mutations may weaken the immune response to lung infections:

• TLR3 mutations increase viral susceptibility

• TLR5 mutations raise the risk of Legionella infections

• Mannose-binding lectin deficiency leads to higher bacterial and fungal infections

4. Tuberculosis (TB)

Only about 10% of those infected with the TB bacteria develop active disease. Genetic variations are believed to play a role in this differential response.

5. Lung Cancer

A strong genetic link has been found on chromosome 15q25.1 (CHRNA3 and CHRNA5), associated with:

• Nicotine addiction

• Increased lung cancer risk

This genetic cluster may influence smoking behaviour and independently increase cancer risk.

6. Pulmonary Embolism

A genetic clotting disorder known as the Factor V Leiden mutation increases the risk of blood clots and pulmonary embolism. Homozygous individuals (two copies of the mutation) are at much higher lifetime risk.

The Role of Genes in Nicotine Addiction

The same CHRNA3 and CHRNA5 gene cluster tied to lung cancer is also linked to nicotine dependence. People with specific variants in these genes may be more likely to:

• Start smoking earlier

• Smoke more cigarettes per day

• Struggle with quitting

This indirectly increases the long-term risk of chronic lung conditions and cancer.

Expert Genetic Lung Care in Nashik

At Dr. Mutha Hospital, we take a personalized approach to lung care, recognizing the influence of genetic background in conditions like asthma, COPD, and cystic fibrosis. Our pulmonologists use advanced diagnostic tools, family history assessments, and genetic counselling to better understand your individual risk and provide tailored treatment.

Whether you’re experiencing symptoms or have a family history of lung disease, early screening can help protect your future lung health.