Genetics of Chronic Sinus Infections

About 10% of the population of Europe and the US have chronic sinus infections, known as sinusitis or rhinosinusitis. While most everyone has known the occasional sinus pain from having a head cold, for some people, this problem continues for months at a time. This article looks at the genetic reasons driving some people to have chronic sinus infections.

Chronic Sinus Infections

Doctors define chronic rhino-sinusitis as having inflamed sinuses (stuffiness, nasal discharge, and changes in the ability to smell) for 12 weeks or more. For a lot of people, this can start with allergies or a cold that turns into a sinus infection that lingers on, never really clearing up and flaring up again periodically. Chronic sinus infections often go hand in hand with allergic rhinitis, frequent colds, atopic dermatitis, and asthma.[ref] Your nose is constantly bringing in bacteria, fungi, and viruses. The first line of defense is the mucous membranes and cilia that clear out the particles coming into the nose.  In someone with chronic sinus infections, could result in persistent inflammation and biofilm formation in the sinus cavities.[ref] In most people though, the acute infection from a pathogen isn't what is continuing to cause chronic sinus problems (defined as 12+ weeks). Instead, the inflammation in the sinuses continues after a triggering episode (allergies, fungus, pathogen, etc).[ref]
Ciliated cells in the nose help to move inhaled pathogens. Creative Commons License. ref

How do your genes influence sinus infections?

Genetics plays a role in the likelihood of having chronic sinus problems. The genetic component can range from genes that influence your inflammatory response to the mutations that cause cystic fibrosis or ciliary diseases.[ref] When researchers investigate how genetics influences the risk of a condition, such as chronic sinus infections, they can go at this a couple of ways. First, they can investigate whether specific genetic variants or mutations are found more commonly in people with the condition. For example, researchers can look at people who carry one copy of the mutations that cause cystic fibrosis to see if they are linked to sinus infections. Or they can investigate genes related to the immune response. Another way to go about looking at genetic connections is to do a 'genome-wide association study'. These research studies involve looking at the whole genome of a large number of people and seeing if there is anything that is different about people with a certain condition. Lots of computing power needed for these studies!

Genetics studies on chronic sinus infections:

Bitter taste receptors show links to the susceptibility of chronic sinus infections in a number of genome-wide studies. While you may be thinking - taste receptors in your nose? - researchers discovered that taste receptors are found throughout the body and perform different functions. In your mouth, taste receptors are chemosensors that are abundant in taste bud cells. But in the nasal and sinus cavities, these same receptors can detect secreted bacterial products and modulate the immune response.[ref] The TAS2R38 gene codes for a bitter taste receptor. A fairly common variant in this gene causes some people to be unable to taste certain bitter flavors. This drives food preferences, to some extent, for things like bitter vegetables, coffee, and scotch.  In the airways, though, it is thought that the TAS2R receptors are important for sensing certain gram-negative bacteria including Pseudomonas aeruginosa, a multi-drug resistant pathogen.[ref] When the TAS2R38 receptor is activated in the nasal passages, it causes the secretion of nitric oxide. The increase in nitric oxide causes two things to happen:  first, it increases the movement of cilia in the nose and second, it can directly kill bacteria.[ref]
Ciliated cells containing T2R38 (bitter taste receptors) cause NO to be released. Creative Commons Image License. ref
Nasal polyps are a risk factor for chronic sinus infections. A genetic variant that causes the ALOX15 gene not to function is associated with a greatly decreased risk of both nasal polyps and chronic sinus infections. ALOX15 gene codes for an enzyme that is important in the metabolism of polyunsaturated fats. It is also important in the inflammatory response to certain pathogens, including pathogens that cause periodontal disease, peritonitis, sepsis, and atherosclerosis.[ref] Cystic fibrosis is a genetic disease causing an alteration to the thickness of mucous in the lungs, gut, and nasal passages. One complication of cystic fibrosis is chronic sinus infections, including with the drug-resistant P. aeruginosa. This is a big problem for people with cystic fibrosis because the pathogen can spread from the nose to the lungs, causing serious lung infections.[ref] Alpha-1 antitrypsin deficiency is another genetic disease linked to an increased risk of chronic sinus infections. Mutations in the SERPINA1 gene cause alterations to the alpha-1 antitrypsin enzyme, which is active in the lungs at all times, but is also part of the immune response against infections. People with Alpha-1 antitrypsin deficiency are at a greater risk for chronic rhinosinusitis.[ref] Inflammatory response, both to pathogens and overall inflammation is also implicated in chronic sinus infections. While many inflammatory cytokine-related genetic variants have been investigated, only a few studies have been replicated in more than one population group. The TNF-alpha variants, though, have found to increase the risk of chronic sinus infections in several studies. The TNF gene codes for tumor necrosis factor-alpha, which is a major player in the regulation of immune cells.

Genetic Variants and Chronic Sinus Infections:

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