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A Genetic Backstory To The Most Common Allergy: Hay Fever

What is hay fever?

Hay fever, also known as allergic rhinitis is an allergic condition that develops as a response to a wide range of indoor and outdoor allergens that can be inhaled.

How do I know if I have hay fever?

Numerous allergens may trigger an allergic response.

The signs and symptoms that follow an allergic exposure, indicating hay fever are:

Sneezing
Nasal itching
Runny or stuffy (congested) nose
Watery and irritable eyes
Cough
Postnasal drip

How do I know that I have hay fever and not the common cold?

There is a high chance of misinterpreting the condition as a common cold due to the close similarities in the symptoms of both; hence, it is necessary to know the difference for appropriate treatment.

There are certain features, in particular, which distinguish the common cold from allergic rhinitis:

Condition	Cause	One Distinguishing symptom	Onset of condition	Duration of condition
Hay fever/Allergic rhinitis	Allergens	Runny nose discharge is watery	Immediately after exposure to the allergen	As long as there is exposure to the allergen
Common cold	Viruses	Runny nose discharge is mucus	1-3 days post-exposure to a virus	4-7 days

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What causes hay fever?

There exists a wide range of allergens that are capable of triggering the allergy, a few of which are:

Indoor allergens- pet dander, dust mites, mold, etc.
Outdoor allergens- grass, trees, flowers, etc.

The underlying cause for allergy has been identified as regular inhalation of an extremely tiny (smaller than the tip of a pin) dry protein called pollen.

Pollens are invisible and are usually smaller than 40 microns in diameter.

They are carried by air and enter the respiratory pathway on inhalation, and as a result, it gets lodged in the nose, causing immediate sneezing, itchy nose, etc.

What is the genetic background of allergic rhinitis?

Though the apparent reason for hay fever is the exposure to pollen, a person's genetic makeup can make them more susceptible to developing this allergy.

A few genes underlying the reason behind an allergic reaction are-

HLADQB1
IL33
SMAD3
IL1R1
TLR1

In hay fever, certain variant forms of the above genes are implicated:

HLADQB1

The gene is a member of the Human Leucocyte Antigen family of genes that is responsible for secreting proteins that trigger an immune response by displaying foreign peptides to the immune system.

The single nucleotide polymorphism in HLADQB1 implicated in hay fever causes hyperactivity of the gene. Thus an immune response is elicited; consequently, harmless pollen is identified as a harmful foreign substance, resulting in an allergy.

Gene	SNP Id	Risk Allele	Implications of risk allele
HLADBQ1	rs9273373	G	Increased activity of immune system, recognizing pollen as an allergen.

IL33

IL33 gene is a part of the interleukin family and is responsible for the activation of various components of the immune system like basophils, eosinophils, and natural killer cells.

A mutation in the gene, found in hay fever leads to increased activity of IL33, thereby increased action of the immune system components, which results in an allergic outcome to exposure of mere pollens.

GENE	SNP Id	Risk allele	Implications of risk allele
IL33	rs72699186	T	Hyper-activation of immune system components.

SMAD3

The SMAD3 gene provides instructions to synthesize the SMAD3 proteins, which upon activation by TGFB protein plays a major role in the activation of various genes, in cellular processes like cell differentiation, proliferation, etc.

A mutation in this gene results in an increased differentiation and proliferation of immune cells.

GENE	RS Id	Risk Allele	Implications of risk allele
SMAD3	rs17294280	G	Increased differentiation and proliferation of immune cells.

TLR1

TLR1 (Toll-Like Receptor 1) encodes pattern-recognition receptors whose role is to recognize external pathogens and thereby activate appropriate immune responses.

The presence of T allele, the risk allele, leads to the sensitivity of pollen, therefore, hyper-activation of the corresponding immune response.